{"gene":"MOV10","run_date":"2026-06-10T02:59:50","timeline":{"discoveries":[{"year":2014,"finding":"MOV10 has ATP-dependent 5' to 3' RNA unwinding activity in vitro and translocates 5' to 3' on mRNA targets. MOV10 helicase mutants are impaired in translocation. MOV10 predominantly binds 3' UTRs upstream of regions predicted to form local secondary structures. MOV10 interacts with UPF1, and PAR-CLIP shows MOV10 and UPF1 bind RNA in close proximity. Knockdown of MOV10 increased mRNA half-lives of MOV10-bound and UPF1-regulated transcripts, implicating MOV10 as an RNA clearance factor in UPF1-mediated mRNA degradation.","method":"In vitro RNA unwinding assay, PAR-CLIP, Co-IP, mRNA half-life measurement, helicase mutant analysis","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro biochemical assay plus mutagenesis plus PAR-CLIP plus mRNA stability measurements in one rigorous study","pmids":["24726324"],"is_preprint":false},{"year":2009,"finding":"MOV10 is present at synapses and is rapidly degraded by the proteasome in an NMDA-receptor-mediated, activity-dependent manner. When MOV10 is suppressed, specific mRNAs (including alpha-CaMKII, Limk1, and Lypla1) enter the polysome compartment, and activity-dependent protein synthesis driven by Lypla1 and alpha-CaMKII 3'UTRs is MOV10- and proteasome-dependent.","method":"Translational trap assay, polysome fractionation, proteasome inhibitor treatment, NMDA-receptor stimulation, photoconvertible translation reporter (Kaede)","journal":"Neuron","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (polysome fractionation, reporter assay, pharmacological inhibition) in a focused study; widely cited and mechanistically precise","pmids":["20064393"],"is_preprint":false},{"year":2014,"finding":"FMRP associates with MOV10 both directly and in an RNA-dependent manner and facilitates MOV10's association with RNAs in brain. MOV10 has a dual function: it facilitates microRNA-mediated translation repression of some mRNAs, but also prevents AGO2 function on a subset of mRNAs co-bound by FMRP, thereby increasing their expression. FMRP binding near MOV10 binding sites prevents MOV10-mediated microRNA suppression.","method":"Co-IP, RNA immunoprecipitation (RIP), iCLIP, reporter assays","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP plus iCLIP plus functional reporter assays establishing bi-directional regulation","pmids":["25464849"],"is_preprint":false},{"year":2012,"finding":"MOV10 severely restricts human LINE-1 (L1), Alu, and SVA retrotransposons. MOV10 associates with the L1 ribonucleoprotein particle and colocalizes with L1 ORF1 protein in stress granules. This inhibitory activity is dependent on intact helicase domains.","method":"Retrotransposition assay, Co-IP/co-fractionation, immunofluorescence colocalization, helicase domain mutant analysis","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — replicated across multiple retrotransposon systems with helicase domain mutagenesis and co-localization; independently replicated in multiple studies","pmids":["23093941"],"is_preprint":false},{"year":2013,"finding":"MOV10 suppresses LINE-1 transposition through its helicase activity; mutating helicase motifs impairs this function. MOV10 post-transcriptionally reduces LINE-1 RNA levels and associates with both LINE-1 RNA and ORF1 protein, indicating MOV10 interacts with LINE-1 RNP to cause RNA degradation.","method":"Retrotransposition assay, helicase motif mutagenesis, RT-qPCR for RNA levels, Co-IP with LINE-1 ORF1","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — helicase mutagenesis combined with RNA quantification and protein interaction assay; consistent with independent reports","pmids":["23754279"],"is_preprint":false},{"year":2010,"finding":"MOV10 (a superfamily-1 RNA helicase and RISC component) inhibits retrovirus replication. When overexpressed in viral producer cells, MOV10 reduces HIV-1 infectivity. MOV10 interacts with HIV-1 nucleocapsid protein in an RNA-dependent manner and is packaged into virions. It blocks HIV-1 replication at a post-entry step. Silencing MOV10 increases HIV-1 infectivity.","method":"Overexpression/knockdown, infectivity assays, Co-IP, virion incorporation western blot","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal gain/loss-of-function plus Co-IP plus virion incorporation; independently replicated by multiple labs","pmids":["20215113"],"is_preprint":false},{"year":2010,"finding":"MOV10 is a P-body-associated protein; its overexpression in virus producer cells inhibits HIV-1 at multiple stages including reducing steady-state Gag protein levels, virus production, and virion infectivity partly by inhibiting reverse transcription. MOV10 is efficiently incorporated into virions. The N-terminal half of MOV10 is required for its HIV inhibitory activity; removing it abolishes activity, whereas helicase mutation or C-terminal truncation retains most inhibitory activity.","method":"Overexpression, siRNA knockdown, infectivity assays, reverse transcription assays, domain truncation/mutation analysis, virion western blot","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 2 / Strong — domain mapping combined with multiple functional assays; independently confirmed by other labs","pmids":["20668078"],"is_preprint":false},{"year":2010,"finding":"Endogenous MOV10 is mostly nuclear in human cells, and a proportion associates with chromatin in an RNA-dependent manner. MOV10 co-purifies and interacts with components of Polycomb-repressive complex 1 (PRC1). ShRNA-mediated knockdown of MOV10 leads to upregulation of the INK4a tumor suppressor, dissociation of PRC1 proteins from the INK4a locus, and reduction in H3K27me3 at that locus.","method":"Co-purification, Co-IP, chromatin fractionation, shRNA knockdown, ChIP for H3K27me3 and PRC1 components","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — co-purification plus ChIP plus shRNA knockdown with defined chromatin phenotype, single lab but multiple orthogonal methods","pmids":["20543829"],"is_preprint":false},{"year":2016,"finding":"MOV10 inhibits influenza A virus replication by interacting (via RNA-mediated interaction) with the nucleoprotein (NP) subunit of the vRNP complex, preventing NP binding to importin-α and causing retention of NP in the cytoplasm, thereby inhibiting nuclear import of NP and vRNP function. This inhibitory effect is independent of MOV10's helicase activity.","method":"MOV10 knockdown, minigenome assay, Co-IP, importin-α binding assay, subcellular fractionation/immunofluorescence","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional minigenome assay plus nuclear import assay plus helicase-independence demonstrated by mutagenesis, single lab","pmids":["26842467"],"is_preprint":false},{"year":2012,"finding":"Endogenous MOV10 suppresses retrotransposition of LTR and non-LTR endogenous retroelements (shown by RNAi-mediated silencing enhancing retrotransposon replication), but RNAi knockdown has no impact on infectious retrovirus particle production, demonstrating natural MOV10 levels specifically regulate endogenous retroelements in somatic cells. MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing (negative finding).","method":"RNAi knockdown, retrotransposition assay, retrovirus infectivity assay, miRNA/siRNA reporter assays","journal":"Retrovirology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockdown with specific phenotypic readouts across multiple element classes; single lab","pmids":["22727223"],"is_preprint":false},{"year":2016,"finding":"MOV10 exhibits antiviral activity against positive- and negative-strand RNA viruses by enhancing type I IFN induction, independent of its helicase function. This activity requires IRF3-mediated IFN induction and downstream IFN receptor signaling. MOV10 specifically requires IKKε (not TBK1) for antiviral activity, and this IFN induction pathway is independent of RIG-I/MAVS. Viral proteases from picornavirus family specifically targeted MOV10 as an immune evasion mechanism.","method":"Genome-edited knockout human cells, IFN reporter assays, viral replication assays, kinase knockdown/knockout experiments","journal":"Journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-edited KO cells plus multiple pathway knockouts; single lab, multiple orthogonal methods","pmids":["27016603"],"is_preprint":false},{"year":2008,"finding":"MOV10 (human homolog of Arabidopsis SDE3 and Drosophila Armitage) interacts with hepatitis delta antigen (HDAg). MOV10 knockdown inhibited HDV replication but not HDAg mRNA translation, supporting a role for MOV10 in RNA-directed transcription rather than translation.","method":"HDAg-interaction screen, MOV10 knockdown, HDV replication assay, translation assay","journal":"Nature structural & molecular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — interaction screen plus functional knockdown with two distinct readouts; single lab","pmids":["18552826"],"is_preprint":false},{"year":2011,"finding":"MOV10 is packaged into HIV-1 virions via binding to the nucleocapsid (NC) basic linker region of Gag; the Gag binding region on MOV10 maps to N-terminal amino acids 261-305 (a Cys-His-rich domain). Packaging also requires nearly all C-terminal helicase motifs. Simultaneous mutation of residues Cys-188, Cys-195, His-199, His-201, and His-202 significantly compromised anti-HIV-1 activity. The minimal antiviral region maps to amino acids 99-949.","method":"Domain deletion/mutagenesis, virion incorporation assay, infectivity assay, structural domain modeling","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic domain mutagenesis with functional readouts; single lab","pmids":["22105071"],"is_preprint":false},{"year":2012,"finding":"APOBEC3G (A3G) counteracts miRNA-mediated translation repression by inhibiting the interaction between MOV10 and AGO2. A3G binds to a C-terminal domain of MOV10 and competitively inhibits AGO2 binding to the same domain. The A3G-MOV10 interaction relies on 7SL RNA; the A3G mutant W127L, which cannot bind 7SL RNA, loses this ability.","method":"Co-IP, domain deletion mapping, reporter assay for miRNA repression, RNA-dependence assay with RNase treatment","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with domain mapping plus functional reporter assay; single lab, multiple methods","pmids":["22791714"],"is_preprint":false},{"year":2018,"finding":"MOV10 interacts with RNASEH2 (identified by proteomics). RNASEH2 and MOV10 co-localize in the nucleus and their interplay restricts L1 retrotransposition. RNASEH2 binds to L1 RNAs in a MOV10-dependent manner. Depletion of either RNASEH2A or MOV10 results in accumulation of L1-specific RNA-DNA hybrids, suggesting they prevent formation of L1 heteroduplexes during retrotransposition.","method":"Proteomic Co-IP, Co-IP, immunofluorescence co-localization, shRNA knockdown, retrotransposition assay, RNA-DNA hybrid detection","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proteomic identification plus Co-IP plus functional knockdown with RNA-DNA hybrid readout; single lab","pmids":["29315404"],"is_preprint":false},{"year":2017,"finding":"MOV10 interacts with IRAV (FLJ11286) in P-bodies of uninfected cells. After dengue virus infection, IRAV and MOV10 (along with Xrn1) localize to the DENV replication complex. Depletion of either IRAV or MOV10 increases dengue viral RNA levels.","method":"Co-IP, immunofluorescence, siRNA knockdown, viral RNA quantification","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus colocalization plus knockdown with viral RNA readout; single lab","pmids":["27974568"],"is_preprint":false},{"year":2019,"finding":"MOV10 restricts hepatitis B virus replication by interacting with HBV RNA and blocking the early step of viral reverse transcription, impairing viral DNA synthesis without affecting viral gene expression or pregenomic RNA encapsidation. Mutation of the helicase domain caused loss of HBV RNA binding and anti-HBV activity.","method":"Overexpression/knockdown, viral DNA quantification, RNA co-IP, helicase domain mutagenesis, Southern blot","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — helicase mutagenesis plus RNA-binding assay plus staged functional analysis; single lab","pmids":["31722967"],"is_preprint":false},{"year":2015,"finding":"MOV10 functions as a co-factor of HIV-1 Rev, interacting with Rev in an RNA-independent manner to enhance nuclear export of viral mRNAs via the Rev/RRE axis. The DEAG-box of MOV10 is required for this enhancement; a DEAG-box mutant shows dominant-negative activity.","method":"Co-IP, nuclear export assay, DEAG-box mutagenesis, Gag protein expression assay","journal":"Virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional mutagenesis and export assay; single lab","pmids":["26379090"],"is_preprint":false},{"year":2019,"finding":"MOV10 is localized to P-bodies in uninfected cells, but during HCV infection it relocalizes to circular structures surrounding cytoplasmic lipid droplets with NS5A and core protein. Mov10 overexpression suppresses HCV RNA and reduces infectivity. The RNA-binding activity of MOV10 is required for HCV inhibition, while P-body localization, helicase, and ATP-binding functions are not required. Endogenous MOV10 promotes HCV replication (CRISPR depletion decreases HCV replication).","method":"Confocal imaging, MOV10 overexpression/CRISPR KO, HCV RNA quantification, infectivity assay, mutagenesis","journal":"FASEB journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR KO plus overexpression plus mutagenesis with localization studies; single lab, multiple methods","pmids":["32496609"],"is_preprint":false},{"year":2021,"finding":"MOV10 is a substrate of the CRL4-DCAF12 ubiquitin ligase; DCAF12 controls MOV10 protein levels via MOV10's C-terminal motif in a proteasome- and CRL-dependent manner. DCAF12 knockout mice show elevated MOV10 levels and produce fewer mature sperm, with imbalances in meiotic markers SCP3 and γ-H2AX.","method":"Co-purification of CRL4-DCAF12 complexes, proteasome inhibitor treatment, CRL inhibitor treatment, DCAF12 KO mouse, western blot","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical Co-purification plus KO mouse phenotype plus pharmacological validation; single lab","pmids":["34065512"],"is_preprint":false},{"year":2017,"finding":"In mouse brain, Mov10 suppresses retroelements in the nucleus by directly inhibiting complementary DNA synthesis. Cytosolic Mov10 binds cytoskeletal mRNAs and regulates neurite outgrowth. Loss of Mov10 in hippocampal neurons (heterozygote mouse) reduces dendritic arborization. Mov10 knockout causes embryonic lethality. Mov10, Fmrp, and Ago2 bind a common set of mRNAs in the brain.","method":"Mov10 KO/heterozygote mouse, retrotransposition/cDNA synthesis assay, RIP-seq, neurite outgrowth assay, behavioral testing","journal":"BMC biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mouse KO/heterozygote with multiple cellular and behavioral readouts; single lab","pmids":["28662698"],"is_preprint":false},{"year":2019,"finding":"In rat cortical synaptoneurosomes, MOV10 forms an inhibitory complex with FMRP and AGO2 on a subset of NMDAR-responsive mRNAs. Upon NMDAR stimulation, MOV10 dissociates from AGO2 and promotes translation of its target mRNAs. FMRP is required to form the MOV10-AGO2 inhibitory complex and to promote translation of MOV10-associated mRNAs. Phosphorylation of FMRP appears to be the switch for NMDAR-mediated translation.","method":"Synaptoneurosome preparation, Co-IP, polysome fractionation, pharmacological NMDAR stimulation, western blot","journal":"Molecular brain","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus polysome profiling plus pharmacological manipulation in native synaptic preparation; single lab","pmids":["31291981"],"is_preprint":false},{"year":2020,"finding":"MOV10 targets the nucleoproteins (N) of emerging high-pathogenic bunyaviruses (including SFTSV) in an RNA-independent manner. MOV10 blocks N polymerization, N-RNA binding, and N-polymerase interaction, thereby disabling RNP assembly. This anti-bunyavirus activity is independent of MOV10's helicase activity and the cellular interferon pathway. The N-terminus of MOV10 binds a 34-amino-acid N-arm domain of N critical for N function.","method":"Mass spectrometry, protein-interaction assays, minigenome assay, MOV10 knockdown/in vivo animal infection, N polymerization/RNA binding assay, domain mapping","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple biochemical assays plus in vivo animal model; single lab","pmids":["33284835"],"is_preprint":false},{"year":2020,"finding":"The N-terminus of MOV10 is required for FMRP-mediated protection of a subset of co-bound mRNAs from AGO association: overexpression of the N-terminus leads to increased levels of endogenous proteins encoded by this co-bound subset. The RGG box of FMRP protects co-bound mRNAs from AGO association. The N-terminus of MOV10 increases RGG box-dependent binding to SC1 RNA G-Quadruplex and is required for neurite outgrowth.","method":"Domain mapping by Co-IP, western blot for protein levels, RNA G-quadruplex binding assay, neurite outgrowth assay, AGO2 RIP","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain mapping plus G-quadruplex assay plus neurite outgrowth functional readout; single lab","pmids":["31740951"],"is_preprint":false},{"year":2023,"finding":"MOV10 recruits the decapping enzyme DCP2 to LINE-1 RNA, forming a complex of MOV10, DCP2, and LINE-1 RNP that exhibits liquid-liquid phase separation (LLPS) properties. DCP2 cooperates with MOV10 to decap LINE-1 RNA, causing LINE-1 RNA degradation and reduced retrotransposition.","method":"Co-IP, phase separation assay, LINE-1 RNA decapping assay, retrotransposition assay, fluorescence microscopy","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus in vitro decapping plus phase separation characterization plus functional retrotransposition assay; single lab","pmids":["37437058"],"is_preprint":false},{"year":2023,"finding":"MOV10 is phosphorylated at serine 970 (S970) at the C-terminus. Phospho-mimic S970D substitution blocks MOV10 unfolding of an RNA G-quadruplex (similar to helicase domain mutation K531A), while the S970A substitution retains unfolding activity. S970D causes decreased expression of MOV10-enhanced CLIP targets in an AGO2-dependent manner. MOV10 activity normally protects mRNAs from AGO2; S970 phosphorylation restricts this protection, resulting in AGO2-mediated mRNA degradation.","method":"Mass spectrometry, site-directed mutagenesis, RNA G-quadruplex unwinding assay, RNA-seq, AGO2 knockdown, Co-IP","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — mass spectrometry identification plus in vitro functional assay plus mutagenesis plus RNA-seq; single lab, multiple orthogonal methods","pmids":["36871759"],"is_preprint":false},{"year":2019,"finding":"MOV10 and MOV10L1 can both resolve RNA G-quadruplex (RG4) structures in vitro, but MOV10L1 does so more efficiently. Both proteins are ATP-dependent. MOV10 does not show preference for binding at a junction between single-stranded RNA and RG4 (in contrast to MOV10L1).","method":"In vitro helicase assay with RG4 substrates, binding assays, ATP hydrolysis assays","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro reconstitution with defined substrates but single lab comparing two paralogs","pmids":["31252377"],"is_preprint":false},{"year":2009,"finding":"MOV10 was isolated as a telomerase-associated protein from porcine testis; it purified with telomerase activity. Anti-MOV10 antibody precipitated telomerase activity from cancer cell extracts and inhibited telomerase activity in vitro. MOV10 binds to the G-rich strand of both single- and double-stranded telomere-sequenced DNA. ChIP assay showed MOV10 binding to telomere regions in vivo.","method":"Protein purification co-purifying telomerase activity, anti-MOV10 immunoprecipitation, in vitro telomerase inhibition, DNA binding assay, ChIP","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP-type approach plus in vitro inhibition assay; single lab, not replicated","pmids":["19665004"],"is_preprint":false},{"year":2019,"finding":"MOV10 is a nucleocytoplasmic protein in spermatogonia. Nuclear MOV10 associates with splicing factors, particularly SRSF1, with intronic binding sites near splice sites. Knockdown of MOV10 impairs miRNA biogenesis (partially via decreased primary transcript levels and/or retention of miRNA via splicing control) and disrupts spermatogonial progenitor cell proliferation and repopulation.","method":"Immunofluorescence, RIP-seq/CLIP-seq, MOV10 knockdown, transplantation experiment, miRNA profiling","journal":"BMC biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — RIP-seq plus knockdown with cellular phenotype; association with splicing factors shown by single method; single lab","pmids":["31088452"],"is_preprint":false},{"year":2021,"finding":"MOV10 interacts with MERS-CoV nucleocapsid (N) protein (confirmed by endogenous Co-IP), colocalizes with N protein in cytoplasmic aggregates, and sequesters viral RNA in these complexes (RNA-IP). MOV10 silencing increases both N protein levels and virus titer. The helicase activity of MOV10 is required for its antiviral effect against MERS-CoV, shown using CRISPR KO cells expressing WT vs. helicase-dead MOV10. MOV10-N interaction is conserved across human CoVs including SARS-CoV-2.","method":"Co-IP (endogenous), RNA immunoprecipitation, CRISPR KO cell lines, WT vs. helicase-dead mutant complementation, viral titer assay","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — endogenous Co-IP plus RNA-IP plus CRISPR KO plus mutagenesis; single lab, multiple methods","pmids":["34517762"],"is_preprint":false},{"year":2013,"finding":"MOV10 and APOBEC3G localization to P-bodies is NOT required for virion incorporation or antiviral activity against HIV-1. A helicase V mutant of MOV10 has significantly reduced P-body localization but still efficiently inhibits viral infectivity via virion incorporation. CRISPR/DDX6-knockdown-disrupted P-bodies confirmed MOV10 antiviral activity without P-body localization. AGO2-mediated RNA-induced silencing is required for MOV10's ability to reduce Gag expression upon overexpression, but NOT for virion incorporation or infectivity effects.","method":"P-body disruption by DDX6 knockdown, helicase V mutant analysis, sucrose gradient sedimentation, AGO2 depletion, infectivity assay","journal":"Journal of virology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple dissection approaches (mutagenesis, P-body disruption, AGO2 depletion) with specific functional readouts; single lab","pmids":["23926332"],"is_preprint":false},{"year":2018,"finding":"MOV10 inhibits PRRSV replication by interacting with the viral nucleocapsid (N) protein in the cytoplasm and retaining N protein in the cytoplasm, preventing its nuclear import. MOV10 does not affect virus attachment or internalization.","method":"Stable MOV10 overexpression, Co-IP, immunofluorescence co-localization, subcellular fractionation, adsorption assay","journal":"Biochemical and biophysical research communications","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Co-IP plus co-localization plus overexpression functional assay; single lab, limited mechanistic depth","pmids":["30172377"],"is_preprint":false},{"year":2022,"finding":"MOV10 forms a complex with UPF1 in mouse testis and primarily binds 3' UTRs of somatically expressed transcripts. Loss of MOV10 in mice results in an altered testis transcriptome and increased LINE-1 retrotransposition in somatic and reproductive tissues in a dosage-dependent manner. MOV10 deficiency reduces reproductive fitness over successive generations.","method":"MOV10 KO mouse (conditional), LINE-1 reporter transgene, RNA-seq, biochemical Co-IP for UPF1 complex","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo mouse KO with LINE-1 reporter transgene plus biochemical complex validation; single lab","pmids":["37126510"],"is_preprint":false},{"year":2017,"finding":"MOV10 inhibits Vif-mediated degradation of APOBEC3G by interfering with assembly of the Vif-CBF-β-Cullin5-ElonginB-ElonginC E3 ubiquitin ligase complex. The DEAG-box of MOV10 is required for this inhibition.","method":"Co-IP for E3 ligase complex components, western blot for A3G levels, DEAG-box mutagenesis, proteasome assay","journal":"Retrovirology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Co-IP with mutagenesis for complex inhibition; single lab, mechanism partially characterized","pmids":["29258557"],"is_preprint":false},{"year":2019,"finding":"MOV10 sequesters influenza A virus RNP in the cytoplasm by interacting with viral NP, and this leads to degradation of viral vRNA. P-body integrity is required for MOV10's antiviral activity. Viral NS1 protein antagonizes MOV10 by interfering with MOV10-NP interaction and promoting MOV10 degradation via the lysosomal pathway.","method":"Co-IP, RNA degradation assay, P-body disruption (DDX6 knockdown), NS1 co-expression, lysosome inhibitor treatment, viral RNA quantification","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus functional P-body disruption plus pharmacological lysosome inhibition; single lab","pmids":["30617221"],"is_preprint":false},{"year":2018,"finding":"Knockdown of maternal Mov10 in Xenopus laevis embryos causes defects in gastrulation, notochord and paraxial mesoderm development, and failure to neurulate. Degradation of the miR-427 target mRNA cyclin A1 (maternal-to-zygotic transition event) is delayed in Mov10 knockdowns. Zygotic Mov10 knockdown impairs head, eye, and brain development.","method":"Translation-blocking morpholino knockdown in Xenopus, RNA-seq, developmental phenotype analysis, cyclin A1 mRNA stability assay","journal":"Developmental dynamics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — morpholino knockdown with specific developmental phenotype plus RNA-seq and mRNA stability readout; single lab","pmids":["29266590"],"is_preprint":false},{"year":2021,"finding":"MOV10 regulates dendritic arborization and NUMA1 mRNA translation in hippocampal neurons. In brain-specific Mov10 KO mice, NUMA1 expression is decreased. Restoration of NUMA1 expression or knockdown of HAUS rescued abnormal dendritic phenotypes in Mov10 KO hippocampal neurons. Enhanced fear memory is observed in Mov10 KO mice.","method":"Brain-specific MOV10 KO mouse, MOV10 CLIP-seq (NUMA1 identified as target), rescue experiments with NUMA1 overexpression and HAUS knockdown, dendritic morphometry","journal":"BMC biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO mouse plus CLIP evidence plus molecular rescue experiments; single lab","pmids":["39915816"],"is_preprint":false},{"year":2025,"finding":"The extended motif II (residues 563-675) and the C-terminal domain (residues 907-1003) of MOV10 cooperate for maximal inhibition of LINE-1 retrotransposition. The extended motif II mediates MOV10-LINE-1 RNA/RNP interaction and is dominant for anti-LINE-1 activity. The C-terminal domain mediates MOV10's association with G3BP1 and formation of cytoplasmic granules, which promotes maximal inhibition.","method":"Domain deletion/truncation mutagenesis, retrotransposition assay, Co-IP for G3BP1, immunofluorescence for granule formation","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic domain mutagenesis with multiple functional readouts; single lab","pmids":["40408535"],"is_preprint":false},{"year":2025,"finding":"The N-terminal domain of MOV10 is functionally distinct from the CH domain of UPF1: it impacts catalytic helicase activity differently and mediates different protein-protein interactions. MOV10 engages the NMD factor UPF2 via its N-terminal regulatory domain, but at a different region than UPF1's CH domain binds UPF2. The MOV10 N-terminal domain dictates its localization to cytoplasmic RNA condensates (P-bodies and stress granules), distinct from UPF1 whose localization is RNA-driven.","method":"In vitro biochemical assays, domain mutagenesis, protein-protein interaction mapping, localization studies","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical reconstitution with domain mutagenesis; single lab, single paper","pmids":["40570961"],"is_preprint":false},{"year":2022,"finding":"MOV10 drives sequestration of LINE-1 ribonucleoprotein complexes into cytoplasmic aggregates, restricting retrotransposition. Combined overexpression of L1 ORF1p and MOV10 is sufficient to create L1 RNP aggregates. In Dicer KO mESCs, MOV10 is upregulated due to loss of direct miRNA regulation, and this elevated MOV10 drives L1 aggregate formation.","method":"Dicer KO mESCs, co-overexpression experiments, immunofluorescence, retrotransposition assay, miRNA regulation of Mov10 3'UTR","journal":"EMBO reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — KO cells plus co-overexpression rescue plus functional retrotransposition readout; single lab","pmids":["35856394"],"is_preprint":false},{"year":2024,"finding":"MOV10 is ISGylated (modified by ISG15), and ISGylated MOV10 enhances IFN-β production/secretion. The deubiquitylase USP24 specifically de-ISGylates MOV10 to negatively regulate the innate immune IFN-I response. USP24 depletion increases ISG15 conjugate accumulation and was identified as a novel ISG15 cross-reactive DUB by activity-based protein profiling.","method":"Activity-based protein profiling (ABPP), in vitro USP24 ISG15-substrate cleavage assay, proteomics (total proteome/GG-peptidome/ISG15 interactome), USP24 depletion, IFN-β reporter assay","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 2 / Weak — multi-omic identification plus in vitro and cell-based validation; preprint, single lab, not yet peer-reviewed","pmids":["bio_10.1101_2024.09.06.611391"],"is_preprint":true},{"year":1994,"finding":"The gb110 gene (MOV10) has a 133-bp intronic enhancer that activates expression ~50-100 fold in undifferentiated F9 embryonal carcinoma cells. This enhancer is inactive in differentiated cells, mediating differentiation-specific downregulation. Four protein-binding sites were identified, including GC/GT-box motifs bound cooperatively by Sp1-related proteins; one GT-box-binding protein is present only in undifferentiated F9 cells.","method":"Transient chloramphenicol acetyltransferase (CAT) reporter assay, DNase I footprinting, gel mobility shift assay, mutational analysis of binding sites","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — functional reporter assay with systematic mutational analysis defining cis-regulatory elements; single lab","pmids":["8065313"],"is_preprint":false}],"current_model":"MOV10 is an ATP-dependent superfamily-1 RNA helicase that unwinds RNA with 5'-to-3' directionality, associates with RISC components (AGO2) and translational regulators (FMRP, UPF1), and acts as a broad-spectrum antiviral and antiretrotransposon factor: it suppresses LINE-1/Alu/SVA retrotransposons and diverse RNA/DNA viruses through mechanisms including viral RNA degradation (recruiting DCP2 for decapping via liquid-liquid phase separation), helicase-dependent RNA clearance to facilitate UPF1-mediated mRNA decay, and helicase-independent blockade of viral nucleoprotein nuclear import; in neurons it undergoes activity-dependent proteasomal degradation downstream of NMDA-receptor stimulation to relieve translational silencing of synaptic mRNAs, and its activity is further regulated by phosphorylation at S970 (restricting helicase activity and enabling AGO2-mediated mRNA degradation) and by CRL4-DCAF12-mediated ubiquitination/proteasomal degradation."},"narrative":{"mechanistic_narrative":"MOV10 is an ATP-dependent superfamily-1 RNA helicase that translocates 5'-to-3' along RNA and acts broadly in post-transcriptional RNA regulation, retroelement restriction, and antiviral defense [PMID:24726324, PMID:23093941]. As an RNA clearance factor it binds 3' UTRs upstream of structured regions and partners with UPF1 to promote decay of co-bound transcripts [PMID:24726324], and in the brain it forms an FMRP- and AGO2-containing inhibitory complex on synaptic mRNAs whose balance is set by FMRP's RGG box and MOV10's N-terminal domain [PMID:25464849, PMID:31291981, PMID:31740951]. MOV10 is a potent suppressor of LINE-1, Alu, and SVA retrotransposons, acting through its helicase domain by associating with the L1 ribonucleoprotein and ORF1p to reduce L1 RNA, sequestering L1 RNP into cytoplasmic/stress-granule aggregates, recruiting the decapping enzyme DCP2 in a phase-separating complex to degrade L1 RNA, and cooperating with RNASEH2 to resolve L1 RNA-DNA hybrids [PMID:23093941, PMID:23754279, PMID:37437058, PMID:29315404, PMID:35856394]. It restricts a wide range of viruses by both helicase-dependent and helicase-independent routes: it is packaged into HIV-1 virions via the nucleocapsid and blocks replication post-entry [PMID:20215113, PMID:20668078, PMID:22105071], degrades influenza vRNA and retains viral nucleoprotein in the cytoplasm to block nuclear import [PMID:26842467, PMID:30617221], and similarly targets the nucleoproteins of bunyaviruses, coronaviruses, and other RNA viruses, in some cases by boosting IRF3/IKKε-driven type I interferon induction [PMID:33284835, PMID:34517762, PMID:27016603]. MOV10 activity is regulated by S970 phosphorylation, which restricts helicase-mediated G-quadruplex unwinding and switches transcripts toward AGO2-mediated degradation [PMID:36871759], and by CRL4-DCAF12-directed ubiquitination and proteasomal turnover [PMID:34065512]. In neurons, MOV10 undergoes NMDA-receptor-driven, proteasome-dependent degradation to relieve translational silencing of synaptic mRNAs [PMID:20064393], and it is required for neurite outgrowth and dendritic arborization through regulation of cytoskeletal and NUMA1 mRNAs [PMID:28662698, PMID:39915816]. MOV10 is essential for development, with knockout causing embryonic lethality in mice and gastrulation/neurulation defects in Xenopus, and it supports reproductive fitness by restraining LINE-1 in the germline [PMID:28662698, PMID:29266590, PMID:37126510].","teleology":[{"year":1994,"claim":"Before any protein function was known, the question was how MOV10 expression is controlled; this established differentiation-coupled transcriptional regulation of the gene.","evidence":"CAT reporter assays, DNase I footprinting, and mutational analysis of a 133-bp intronic enhancer in F9 embryonal carcinoma cells","pmids":["8065313"],"confidence":"Medium","gaps":["Does not address the protein's molecular function","Identity of the undifferentiated-cell-specific GT-box factor unresolved"]},{"year":2008,"claim":"The first functional clue placed MOV10 in RNA-directed processes; its requirement for HDV replication but not HDAg translation implicated it in RNA-templated transcription rather than translation.","evidence":"HDAg-interaction screen with MOV10 knockdown and separate HDV replication and translation readouts","pmids":["18552826"],"confidence":"Medium","gaps":["Helicase activity not directly tested here","Mechanism of action on HDV RNA undefined"]},{"year":2009,"claim":"Two independent contexts established MOV10 as a regulated RNA-handling factor: activity-dependent proteasomal degradation at synapses controlling local translation, and a contested telomerase association.","evidence":"Synaptic translational trap, polysome fractionation, proteasome inhibition and NMDAR stimulation in neurons; separately, co-purification of telomerase activity with anti-MOV10 IP and telomere DNA binding","pmids":["20064393","19665004"],"confidence":"High","gaps":["The telomerase association (idx 27) is Low-confidence, single-lab, and not replicated","Direct helicase action on the synaptic target mRNAs not shown in 2009"]},{"year":2010,"claim":"MOV10 was defined as a broad retroviral restriction factor and a nuclear chromatin-associated regulator, establishing its antiviral identity and a PRC1-linked epigenetic role.","evidence":"Reciprocal overexpression/knockdown HIV-1 infectivity assays, virion incorporation, and domain mapping; plus chromatin fractionation, PRC1 co-IP and ChIP at the INK4a locus","pmids":["20215113","20668078","20543829"],"confidence":"High","gaps":["N-terminal vs helicase contributions to HIV restriction only partly resolved","Mechanism of PRC1 recruitment to chromatin undefined"]},{"year":2012,"claim":"MOV10 was established as a helicase-dependent restrictor of endogenous retroelements and its interface with the RISC/APOBEC3G machinery was mapped, distinguishing antiretroelement from antiretrovirus activity.","evidence":"Retrotransposition assays across L1/Alu/SVA with helicase mutants and L1 RNP co-IP; RNAi specificity for endogenous elements; APOBEC3G domain-mapped competition for AGO2 binding via 7SL RNA","pmids":["23093941","22727223","22791714","22105071"],"confidence":"High","gaps":["Exact step in retrotransposition blocked not fully defined","Whether RISC association is required for antiretroelement activity unresolved"]},{"year":2013,"claim":"Mechanistic dissection showed MOV10 suppresses L1 by helicase-dependent reduction of L1 RNA, and clarified that P-body localization is dispensable for HIV restriction.","evidence":"Helicase-motif mutagenesis with L1 RNA quantification and ORF1 co-IP; P-body disruption by DDX6 knockdown and helicase-V mutant analysis with HIV infectivity readouts","pmids":["23754279","23926332"],"confidence":"High","gaps":["Nuclease/effector that degrades L1 RNA not identified in 2013","How helicase translocation triggers RNA degradation unclear"]},{"year":2014,"claim":"Biochemical reconstitution and CLIP defined MOV10's directional helicase activity and its role as an RNA clearance factor for UPF1-mediated decay, and revealed a dual relationship with the miRNA/FMRP machinery.","evidence":"In vitro 5'-to-3' unwinding with helicase mutants, PAR-CLIP, UPF1 co-IP and mRNA half-life measurements; reciprocal FMRP co-IP, iCLIP and reporter assays","pmids":["24726324","25464849"],"confidence":"High","gaps":["How MOV10 both promotes and antagonizes AGO2 on different transcripts not mechanistically resolved","Determinants of UPF1 vs FMRP coupling unknown"]},{"year":2016,"claim":"Helicase-independent antiviral modes were established: cytoplasmic retention of influenza nucleoprotein blocking nuclear import, and IFN-pathway amplification via IRF3/IKKε independent of RIG-I/MAVS.","evidence":"Knockdown/KO with minigenome, importin-α binding and fractionation assays for influenza NP; IFN reporter and kinase KO experiments for broad RNA-virus restriction","pmids":["26842467","27016603"],"confidence":"Medium","gaps":["How MOV10 activates IKKε specifically is undefined","Connection between NP sequestration and IFN induction unclear"]},{"year":2018,"claim":"A nuclear partner for L1 restriction was identified, linking MOV10 to RNASEH2-dependent resolution of L1 RNA-DNA hybrids.","evidence":"Proteomic co-IP, nuclear co-localization, shRNA knockdown, retrotransposition and RNA-DNA hybrid detection","pmids":["29315404"],"confidence":"Medium","gaps":["Order of MOV10 and RNASEH2 action on hybrids not established","Whether helicase activity feeds hybrid formation unclear"]},{"year":2019,"claim":"In vivo and biochemical work established MOV10's essential developmental and neuronal roles, refined its synaptic FMRP/AGO2 switch, and extended antiviral targeting to HBV.","evidence":"Mov10 KO/heterozygote mice (embryonic lethality, RIP-seq, neurite outgrowth), synaptoneurosome co-IP/polysome NMDAR stimulation, N-terminus/RGG-box G-quadruplex mapping, and HBV helicase-mutant RNA-binding assays","pmids":["28662698","31291981","31740951","31722967","31252377"],"confidence":"Medium","gaps":["In vivo function of helicase activity in neurons not isolated","Kinase responsible for the FMRP/MOV10 phospho-switch unidentified"]},{"year":2020,"claim":"MOV10 was shown to disable viral nucleoprotein assembly across diverse viruses and to relocalize to viral replication sites, defining a recurring nucleoprotein-targeting antiviral strategy.","evidence":"Mass spectrometry, N-polymerization/RNA-binding and minigenome assays with in vivo infection for bunyaviruses; CRISPR KO and mutagenesis for HCV with lipid-droplet relocalization imaging","pmids":["33284835","32496609"],"confidence":"Medium","gaps":["Why MOV10 is proviral for HCV but antiviral for most viruses unresolved","Structural basis of N-arm binding limited to one virus family"]},{"year":2021,"claim":"MOV10 turnover was placed under CRL4-DCAF12 control with a germline phenotype, and helicase-dependent coronavirus restriction plus a NUMA1-dependent dendritic role were established.","evidence":"CRL4-DCAF12 co-purification with DCAF12 KO mice; CRISPR KO/helicase-dead complementation for MERS-CoV with RNA-IP; brain-specific Mov10 KO with NUMA1/HAUS rescue (idx 36 reported 2025)","pmids":["34065512","34517762"],"confidence":"Medium","gaps":["Signals controlling DCAF12-mediated MOV10 degradation unknown","Link between MOV10 levels and meiotic progression not mechanistic"]},{"year":2023,"claim":"The L1-clearance effector and a regulatory phospho-switch were defined: MOV10 recruits DCP2 to decap L1 RNA in a phase-separating complex, and S970 phosphorylation restricts helicase activity to redirect transcripts toward AGO2 degradation.","evidence":"Co-IP, phase-separation and in vitro decapping assays with retrotransposition readout; mass-spectrometry-identified S970 with G-quadruplex unwinding assays, RNA-seq and AGO2 knockdown","pmids":["37437058","36871759"],"confidence":"Medium","gaps":["Kinase phosphorylating S970 not identified","How phase separation couples to decapping efficiency unresolved"]},{"year":2025,"claim":"Domain-level dissection separated MOV10's helicase/RNP-binding and granule-forming functions and distinguished its N-terminal regulatory domain from the UPF1 CH domain in NMD coupling.","evidence":"Domain truncation/mutagenesis with retrotransposition and G3BP1 co-IP for L1 restriction; in vitro biochemistry and interaction mapping with UPF2/UPF1","pmids":["40408535","40570961"],"confidence":"Medium","gaps":["Structural basis of MOV10-UPF2 engagement not solved","How granule formation enhances catalytic restriction unclear"]},{"year":null,"claim":"How MOV10 selects between its opposing outputs — protecting versus degrading bound mRNAs, restricting versus assisting viruses, and acting via helicase-dependent versus helicase-independent routes — remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unifying model for substrate/context selection","Upstream kinases for S970 and the synaptic FMRP switch unidentified","Structural mechanism of nucleoprotein sequestration vs RNA unwinding undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,2,4,16,26]},{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[0,24,26]},{"term_id":"GO:0140657","term_label":"ATP-dependent activity","supporting_discovery_ids":[0,26]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,13,33]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[27]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[7,14,28]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[8,31,34]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[6,15,18,34]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[7]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,2,24,25]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[5,8,10,22,29]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[5,16,18,29]},{"term_id":"R-HSA-112316","term_label":"Neuronal System","supporting_discovery_ids":[1,20,21,36]}],"complexes":["RISC (with AGO2)","MOV10-FMRP-AGO2 inhibitory complex","MOV10-UPF1 complex","PRC1"],"partners":["UPF1","FMRP","AGO2","DCP2","RNASEH2","G3BP1","UPF2","APOBEC3G"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9HCE1","full_name":"Helicase MOV-10","aliases":["Armitage homolog","Moloney leukemia virus 10 protein"],"length_aa":1003,"mass_kda":113.7,"function":"5' to 3' RNA helicase that is involved in a number of cellular roles ranging from mRNA metabolism and translation, modulation of viral infectivity, inhibition of retrotransposition, or regulation of synaptic transmission (PubMed:23093941). Plays an important role in innate antiviral immunity by promoting type I interferon production (PubMed:27016603, PubMed:27974568, PubMed:35157734). Mechanistically, specifically uses IKKepsilon/IKBKE as the mediator kinase for IRF3 activation (PubMed:27016603, PubMed:35157734). Blocks HIV-1 virus replication at a post-entry step (PubMed:20215113). Counteracts HIV-1 Vif-mediated degradation of APOBEC3G through its helicase activity by interfering with the ubiquitin-proteasome pathway (PubMed:29258557). Also inhibits hepatitis B virus/HBV replication by interacting with HBV RNA and thereby inhibiting the early step of viral reverse transcription (PubMed:31722967). Contributes to UPF1 mRNA target degradation by translocation along 3' UTRs (PubMed:24726324). Required for microRNA (miRNA)-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:16289642, PubMed:17507929, PubMed:22791714). In cooperation with FMR1, regulates miRNA-mediated translational repression by AGO2 (PubMed:25464849). Restricts retrotransposition of long interspersed element-1 (LINE-1) in cooperation with TUT4 and TUT7 counteracting the RNA chaperonne activity of L1RE1 (PubMed:23093941, PubMed:30122351). Facilitates LINE-1 uridylation by TUT4 and TUT7 (PubMed:30122351). Required for embryonic viability and for normal central nervous system development and function. Plays two critical roles in early brain development: suppresses retroelements in the nucleus by directly inhibiting cDNA synthesis, while regulates cytoskeletal mRNAs to influence neurite outgrowth in the cytosol (By similarity). May function as a messenger ribonucleoprotein (mRNP) clearance factor (PubMed:24726324) (Microbial infection) Required for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). Interacts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription","subcellular_location":"Cytoplasm, P-body; Cytoplasm, Cytoplasmic ribonucleoprotein granule; Cytoplasm, Stress granule; Nucleus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q9HCE1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MOV10","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CLTA","stoichiometry":0.2},{"gene":"FKBP5","stoichiometry":0.2},{"gene":"IGF2BP1","stoichiometry":0.2},{"gene":"UPF1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MOV10","total_profiled":1310},"omim":[{"mim_id":"620087","title":"DDB1- AND CUL4-ASSOCIATED FACTOR 12; DCAF12","url":"https://www.omim.org/entry/620087"},{"mim_id":"619878","title":"SPERMATOGENIC FAILURE 73; SPGF73","url":"https://www.omim.org/entry/619878"},{"mim_id":"610742","title":"MOV10 RISC COMPLEX RNA HELICASE; MOV10","url":"https://www.omim.org/entry/610742"},{"mim_id":"610740","title":"TRINUCLEOTIDE REPEAT-CONTAINING GENE 6B; TNRC6B","url":"https://www.omim.org/entry/610740"},{"mim_id":"605794","title":"MOV10-LIKE RISC COMPLEX RNA HELICASE 1; MOV10L1","url":"https://www.omim.org/entry/605794"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MOV10"},"hgnc":{"alias_symbol":["gb110","MGC2948","fSAP113"],"prev_symbol":[]},"alphafold":{"accession":"Q9HCE1","domains":[{"cath_id":"-","chopping":"6-75","consensus_level":"high","plddt":84.6557,"start":6,"end":75},{"cath_id":"2.60.40.10","chopping":"108-242","consensus_level":"high","plddt":81.5152,"start":108,"end":242},{"cath_id":"2.40.30.230","chopping":"271-279_361-449","consensus_level":"medium","plddt":85.3208,"start":271,"end":449},{"cath_id":"3.40.50.300","chopping":"484-728","consensus_level":"high","plddt":93.6196,"start":484,"end":728},{"cath_id":"3.40.50.300","chopping":"736-812_822-959","consensus_level":"high","plddt":86.2786,"start":736,"end":959}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9HCE1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9HCE1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9HCE1-F1-predicted_aligned_error_v6.png","plddt_mean":81.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MOV10","jax_strain_url":"https://www.jax.org/strain/search?query=MOV10"},"sequence":{"accession":"Q9HCE1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9HCE1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9HCE1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9HCE1"}},"corpus_meta":[{"pmid":"20064393","id":"PMC_20064393","title":"A 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helicase is a dosage-dependent host restriction factor for LINE1 retrotransposition in mice.","date":"2023","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/37126510","citation_count":6,"is_preprint":false},{"pmid":"29218433","id":"PMC_29218433","title":"s8ORF2 protein of infectious salmon anaemia virus is a RNA-silencing suppressor and interacts with Salmon salar Mov10 (SsMov10) of the host RNAi machinery.","date":"2017","source":"Virus genes","url":"https://pubmed.ncbi.nlm.nih.gov/29218433","citation_count":5,"is_preprint":false},{"pmid":"36871759","id":"PMC_36871759","title":"Serine 970 of RNA helicase MOV10 is phosphorylated and controls unfolding activity and fate of mRNAs targeted for AGO2-mediated silencing.","date":"2023","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/36871759","citation_count":4,"is_preprint":false},{"pmid":"39450567","id":"PMC_39450567","title":"S100A16 stabilizes the ITGA3‑mediated ECM‑receptor 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MOV10 helicase mutants are impaired in translocation. MOV10 predominantly binds 3' UTRs upstream of regions predicted to form local secondary structures. MOV10 interacts with UPF1, and PAR-CLIP shows MOV10 and UPF1 bind RNA in close proximity. Knockdown of MOV10 increased mRNA half-lives of MOV10-bound and UPF1-regulated transcripts, implicating MOV10 as an RNA clearance factor in UPF1-mediated mRNA degradation.\",\n      \"method\": \"In vitro RNA unwinding assay, PAR-CLIP, Co-IP, mRNA half-life measurement, helicase mutant analysis\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro biochemical assay plus mutagenesis plus PAR-CLIP plus mRNA stability measurements in one rigorous study\",\n      \"pmids\": [\"24726324\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"MOV10 is present at synapses and is rapidly degraded by the proteasome in an NMDA-receptor-mediated, activity-dependent manner. When MOV10 is suppressed, specific mRNAs (including alpha-CaMKII, Limk1, and Lypla1) enter the polysome compartment, and activity-dependent protein synthesis driven by Lypla1 and alpha-CaMKII 3'UTRs is MOV10- and proteasome-dependent.\",\n      \"method\": \"Translational trap assay, polysome fractionation, proteasome inhibitor treatment, NMDA-receptor stimulation, photoconvertible translation reporter (Kaede)\",\n      \"journal\": \"Neuron\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (polysome fractionation, reporter assay, pharmacological inhibition) in a focused study; widely cited and mechanistically precise\",\n      \"pmids\": [\"20064393\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"FMRP associates with MOV10 both directly and in an RNA-dependent manner and facilitates MOV10's association with RNAs in brain. MOV10 has a dual function: it facilitates microRNA-mediated translation repression of some mRNAs, but also prevents AGO2 function on a subset of mRNAs co-bound by FMRP, thereby increasing their expression. FMRP binding near MOV10 binding sites prevents MOV10-mediated microRNA suppression.\",\n      \"method\": \"Co-IP, RNA immunoprecipitation (RIP), iCLIP, reporter assays\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP plus iCLIP plus functional reporter assays establishing bi-directional regulation\",\n      \"pmids\": [\"25464849\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"MOV10 severely restricts human LINE-1 (L1), Alu, and SVA retrotransposons. MOV10 associates with the L1 ribonucleoprotein particle and colocalizes with L1 ORF1 protein in stress granules. This inhibitory activity is dependent on intact helicase domains.\",\n      \"method\": \"Retrotransposition assay, Co-IP/co-fractionation, immunofluorescence colocalization, helicase domain mutant analysis\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — replicated across multiple retrotransposon systems with helicase domain mutagenesis and co-localization; independently replicated in multiple studies\",\n      \"pmids\": [\"23093941\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"MOV10 suppresses LINE-1 transposition through its helicase activity; mutating helicase motifs impairs this function. MOV10 post-transcriptionally reduces LINE-1 RNA levels and associates with both LINE-1 RNA and ORF1 protein, indicating MOV10 interacts with LINE-1 RNP to cause RNA degradation.\",\n      \"method\": \"Retrotransposition assay, helicase motif mutagenesis, RT-qPCR for RNA levels, Co-IP with LINE-1 ORF1\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — helicase mutagenesis combined with RNA quantification and protein interaction assay; consistent with independent reports\",\n      \"pmids\": [\"23754279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"MOV10 (a superfamily-1 RNA helicase and RISC component) inhibits retrovirus replication. When overexpressed in viral producer cells, MOV10 reduces HIV-1 infectivity. MOV10 interacts with HIV-1 nucleocapsid protein in an RNA-dependent manner and is packaged into virions. It blocks HIV-1 replication at a post-entry step. Silencing MOV10 increases HIV-1 infectivity.\",\n      \"method\": \"Overexpression/knockdown, infectivity assays, Co-IP, virion incorporation western blot\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal gain/loss-of-function plus Co-IP plus virion incorporation; independently replicated by multiple labs\",\n      \"pmids\": [\"20215113\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"MOV10 is a P-body-associated protein; its overexpression in virus producer cells inhibits HIV-1 at multiple stages including reducing steady-state Gag protein levels, virus production, and virion infectivity partly by inhibiting reverse transcription. MOV10 is efficiently incorporated into virions. The N-terminal half of MOV10 is required for its HIV inhibitory activity; removing it abolishes activity, whereas helicase mutation or C-terminal truncation retains most inhibitory activity.\",\n      \"method\": \"Overexpression, siRNA knockdown, infectivity assays, reverse transcription assays, domain truncation/mutation analysis, virion western blot\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — domain mapping combined with multiple functional assays; independently confirmed by other labs\",\n      \"pmids\": [\"20668078\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Endogenous MOV10 is mostly nuclear in human cells, and a proportion associates with chromatin in an RNA-dependent manner. MOV10 co-purifies and interacts with components of Polycomb-repressive complex 1 (PRC1). ShRNA-mediated knockdown of MOV10 leads to upregulation of the INK4a tumor suppressor, dissociation of PRC1 proteins from the INK4a locus, and reduction in H3K27me3 at that locus.\",\n      \"method\": \"Co-purification, Co-IP, chromatin fractionation, shRNA knockdown, ChIP for H3K27me3 and PRC1 components\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-purification plus ChIP plus shRNA knockdown with defined chromatin phenotype, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"20543829\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"MOV10 inhibits influenza A virus replication by interacting (via RNA-mediated interaction) with the nucleoprotein (NP) subunit of the vRNP complex, preventing NP binding to importin-α and causing retention of NP in the cytoplasm, thereby inhibiting nuclear import of NP and vRNP function. This inhibitory effect is independent of MOV10's helicase activity.\",\n      \"method\": \"MOV10 knockdown, minigenome assay, Co-IP, importin-α binding assay, subcellular fractionation/immunofluorescence\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional minigenome assay plus nuclear import assay plus helicase-independence demonstrated by mutagenesis, single lab\",\n      \"pmids\": [\"26842467\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Endogenous MOV10 suppresses retrotransposition of LTR and non-LTR endogenous retroelements (shown by RNAi-mediated silencing enhancing retrotransposon replication), but RNAi knockdown has no impact on infectious retrovirus particle production, demonstrating natural MOV10 levels specifically regulate endogenous retroelements in somatic cells. MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing (negative finding).\",\n      \"method\": \"RNAi knockdown, retrotransposition assay, retrovirus infectivity assay, miRNA/siRNA reporter assays\",\n      \"journal\": \"Retrovirology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockdown with specific phenotypic readouts across multiple element classes; single lab\",\n      \"pmids\": [\"22727223\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"MOV10 exhibits antiviral activity against positive- and negative-strand RNA viruses by enhancing type I IFN induction, independent of its helicase function. This activity requires IRF3-mediated IFN induction and downstream IFN receptor signaling. MOV10 specifically requires IKKε (not TBK1) for antiviral activity, and this IFN induction pathway is independent of RIG-I/MAVS. Viral proteases from picornavirus family specifically targeted MOV10 as an immune evasion mechanism.\",\n      \"method\": \"Genome-edited knockout human cells, IFN reporter assays, viral replication assays, kinase knockdown/knockout experiments\",\n      \"journal\": \"Journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-edited KO cells plus multiple pathway knockouts; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"27016603\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"MOV10 (human homolog of Arabidopsis SDE3 and Drosophila Armitage) interacts with hepatitis delta antigen (HDAg). MOV10 knockdown inhibited HDV replication but not HDAg mRNA translation, supporting a role for MOV10 in RNA-directed transcription rather than translation.\",\n      \"method\": \"HDAg-interaction screen, MOV10 knockdown, HDV replication assay, translation assay\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — interaction screen plus functional knockdown with two distinct readouts; single lab\",\n      \"pmids\": [\"18552826\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"MOV10 is packaged into HIV-1 virions via binding to the nucleocapsid (NC) basic linker region of Gag; the Gag binding region on MOV10 maps to N-terminal amino acids 261-305 (a Cys-His-rich domain). Packaging also requires nearly all C-terminal helicase motifs. Simultaneous mutation of residues Cys-188, Cys-195, His-199, His-201, and His-202 significantly compromised anti-HIV-1 activity. The minimal antiviral region maps to amino acids 99-949.\",\n      \"method\": \"Domain deletion/mutagenesis, virion incorporation assay, infectivity assay, structural domain modeling\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic domain mutagenesis with functional readouts; single lab\",\n      \"pmids\": [\"22105071\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"APOBEC3G (A3G) counteracts miRNA-mediated translation repression by inhibiting the interaction between MOV10 and AGO2. A3G binds to a C-terminal domain of MOV10 and competitively inhibits AGO2 binding to the same domain. The A3G-MOV10 interaction relies on 7SL RNA; the A3G mutant W127L, which cannot bind 7SL RNA, loses this ability.\",\n      \"method\": \"Co-IP, domain deletion mapping, reporter assay for miRNA repression, RNA-dependence assay with RNase treatment\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with domain mapping plus functional reporter assay; single lab, multiple methods\",\n      \"pmids\": [\"22791714\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MOV10 interacts with RNASEH2 (identified by proteomics). RNASEH2 and MOV10 co-localize in the nucleus and their interplay restricts L1 retrotransposition. RNASEH2 binds to L1 RNAs in a MOV10-dependent manner. Depletion of either RNASEH2A or MOV10 results in accumulation of L1-specific RNA-DNA hybrids, suggesting they prevent formation of L1 heteroduplexes during retrotransposition.\",\n      \"method\": \"Proteomic Co-IP, Co-IP, immunofluorescence co-localization, shRNA knockdown, retrotransposition assay, RNA-DNA hybrid detection\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proteomic identification plus Co-IP plus functional knockdown with RNA-DNA hybrid readout; single lab\",\n      \"pmids\": [\"29315404\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"MOV10 interacts with IRAV (FLJ11286) in P-bodies of uninfected cells. After dengue virus infection, IRAV and MOV10 (along with Xrn1) localize to the DENV replication complex. Depletion of either IRAV or MOV10 increases dengue viral RNA levels.\",\n      \"method\": \"Co-IP, immunofluorescence, siRNA knockdown, viral RNA quantification\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus colocalization plus knockdown with viral RNA readout; single lab\",\n      \"pmids\": [\"27974568\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MOV10 restricts hepatitis B virus replication by interacting with HBV RNA and blocking the early step of viral reverse transcription, impairing viral DNA synthesis without affecting viral gene expression or pregenomic RNA encapsidation. Mutation of the helicase domain caused loss of HBV RNA binding and anti-HBV activity.\",\n      \"method\": \"Overexpression/knockdown, viral DNA quantification, RNA co-IP, helicase domain mutagenesis, Southern blot\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — helicase mutagenesis plus RNA-binding assay plus staged functional analysis; single lab\",\n      \"pmids\": [\"31722967\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"MOV10 functions as a co-factor of HIV-1 Rev, interacting with Rev in an RNA-independent manner to enhance nuclear export of viral mRNAs via the Rev/RRE axis. The DEAG-box of MOV10 is required for this enhancement; a DEAG-box mutant shows dominant-negative activity.\",\n      \"method\": \"Co-IP, nuclear export assay, DEAG-box mutagenesis, Gag protein expression assay\",\n      \"journal\": \"Virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional mutagenesis and export assay; single lab\",\n      \"pmids\": [\"26379090\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MOV10 is localized to P-bodies in uninfected cells, but during HCV infection it relocalizes to circular structures surrounding cytoplasmic lipid droplets with NS5A and core protein. Mov10 overexpression suppresses HCV RNA and reduces infectivity. The RNA-binding activity of MOV10 is required for HCV inhibition, while P-body localization, helicase, and ATP-binding functions are not required. Endogenous MOV10 promotes HCV replication (CRISPR depletion decreases HCV replication).\",\n      \"method\": \"Confocal imaging, MOV10 overexpression/CRISPR KO, HCV RNA quantification, infectivity assay, mutagenesis\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR KO plus overexpression plus mutagenesis with localization studies; single lab, multiple methods\",\n      \"pmids\": [\"32496609\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MOV10 is a substrate of the CRL4-DCAF12 ubiquitin ligase; DCAF12 controls MOV10 protein levels via MOV10's C-terminal motif in a proteasome- and CRL-dependent manner. DCAF12 knockout mice show elevated MOV10 levels and produce fewer mature sperm, with imbalances in meiotic markers SCP3 and γ-H2AX.\",\n      \"method\": \"Co-purification of CRL4-DCAF12 complexes, proteasome inhibitor treatment, CRL inhibitor treatment, DCAF12 KO mouse, western blot\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical Co-purification plus KO mouse phenotype plus pharmacological validation; single lab\",\n      \"pmids\": [\"34065512\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"In mouse brain, Mov10 suppresses retroelements in the nucleus by directly inhibiting complementary DNA synthesis. Cytosolic Mov10 binds cytoskeletal mRNAs and regulates neurite outgrowth. Loss of Mov10 in hippocampal neurons (heterozygote mouse) reduces dendritic arborization. Mov10 knockout causes embryonic lethality. Mov10, Fmrp, and Ago2 bind a common set of mRNAs in the brain.\",\n      \"method\": \"Mov10 KO/heterozygote mouse, retrotransposition/cDNA synthesis assay, RIP-seq, neurite outgrowth assay, behavioral testing\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mouse KO/heterozygote with multiple cellular and behavioral readouts; single lab\",\n      \"pmids\": [\"28662698\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In rat cortical synaptoneurosomes, MOV10 forms an inhibitory complex with FMRP and AGO2 on a subset of NMDAR-responsive mRNAs. Upon NMDAR stimulation, MOV10 dissociates from AGO2 and promotes translation of its target mRNAs. FMRP is required to form the MOV10-AGO2 inhibitory complex and to promote translation of MOV10-associated mRNAs. Phosphorylation of FMRP appears to be the switch for NMDAR-mediated translation.\",\n      \"method\": \"Synaptoneurosome preparation, Co-IP, polysome fractionation, pharmacological NMDAR stimulation, western blot\",\n      \"journal\": \"Molecular brain\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus polysome profiling plus pharmacological manipulation in native synaptic preparation; single lab\",\n      \"pmids\": [\"31291981\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MOV10 targets the nucleoproteins (N) of emerging high-pathogenic bunyaviruses (including SFTSV) in an RNA-independent manner. MOV10 blocks N polymerization, N-RNA binding, and N-polymerase interaction, thereby disabling RNP assembly. This anti-bunyavirus activity is independent of MOV10's helicase activity and the cellular interferon pathway. The N-terminus of MOV10 binds a 34-amino-acid N-arm domain of N critical for N function.\",\n      \"method\": \"Mass spectrometry, protein-interaction assays, minigenome assay, MOV10 knockdown/in vivo animal infection, N polymerization/RNA binding assay, domain mapping\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple biochemical assays plus in vivo animal model; single lab\",\n      \"pmids\": [\"33284835\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The N-terminus of MOV10 is required for FMRP-mediated protection of a subset of co-bound mRNAs from AGO association: overexpression of the N-terminus leads to increased levels of endogenous proteins encoded by this co-bound subset. The RGG box of FMRP protects co-bound mRNAs from AGO association. The N-terminus of MOV10 increases RGG box-dependent binding to SC1 RNA G-Quadruplex and is required for neurite outgrowth.\",\n      \"method\": \"Domain mapping by Co-IP, western blot for protein levels, RNA G-quadruplex binding assay, neurite outgrowth assay, AGO2 RIP\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain mapping plus G-quadruplex assay plus neurite outgrowth functional readout; single lab\",\n      \"pmids\": [\"31740951\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MOV10 recruits the decapping enzyme DCP2 to LINE-1 RNA, forming a complex of MOV10, DCP2, and LINE-1 RNP that exhibits liquid-liquid phase separation (LLPS) properties. DCP2 cooperates with MOV10 to decap LINE-1 RNA, causing LINE-1 RNA degradation and reduced retrotransposition.\",\n      \"method\": \"Co-IP, phase separation assay, LINE-1 RNA decapping assay, retrotransposition assay, fluorescence microscopy\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus in vitro decapping plus phase separation characterization plus functional retrotransposition assay; single lab\",\n      \"pmids\": [\"37437058\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"MOV10 is phosphorylated at serine 970 (S970) at the C-terminus. Phospho-mimic S970D substitution blocks MOV10 unfolding of an RNA G-quadruplex (similar to helicase domain mutation K531A), while the S970A substitution retains unfolding activity. S970D causes decreased expression of MOV10-enhanced CLIP targets in an AGO2-dependent manner. MOV10 activity normally protects mRNAs from AGO2; S970 phosphorylation restricts this protection, resulting in AGO2-mediated mRNA degradation.\",\n      \"method\": \"Mass spectrometry, site-directed mutagenesis, RNA G-quadruplex unwinding assay, RNA-seq, AGO2 knockdown, Co-IP\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — mass spectrometry identification plus in vitro functional assay plus mutagenesis plus RNA-seq; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"36871759\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MOV10 and MOV10L1 can both resolve RNA G-quadruplex (RG4) structures in vitro, but MOV10L1 does so more efficiently. Both proteins are ATP-dependent. MOV10 does not show preference for binding at a junction between single-stranded RNA and RG4 (in contrast to MOV10L1).\",\n      \"method\": \"In vitro helicase assay with RG4 substrates, binding assays, ATP hydrolysis assays\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro reconstitution with defined substrates but single lab comparing two paralogs\",\n      \"pmids\": [\"31252377\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"MOV10 was isolated as a telomerase-associated protein from porcine testis; it purified with telomerase activity. Anti-MOV10 antibody precipitated telomerase activity from cancer cell extracts and inhibited telomerase activity in vitro. MOV10 binds to the G-rich strand of both single- and double-stranded telomere-sequenced DNA. ChIP assay showed MOV10 binding to telomere regions in vivo.\",\n      \"method\": \"Protein purification co-purifying telomerase activity, anti-MOV10 immunoprecipitation, in vitro telomerase inhibition, DNA binding assay, ChIP\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP-type approach plus in vitro inhibition assay; single lab, not replicated\",\n      \"pmids\": [\"19665004\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MOV10 is a nucleocytoplasmic protein in spermatogonia. Nuclear MOV10 associates with splicing factors, particularly SRSF1, with intronic binding sites near splice sites. Knockdown of MOV10 impairs miRNA biogenesis (partially via decreased primary transcript levels and/or retention of miRNA via splicing control) and disrupts spermatogonial progenitor cell proliferation and repopulation.\",\n      \"method\": \"Immunofluorescence, RIP-seq/CLIP-seq, MOV10 knockdown, transplantation experiment, miRNA profiling\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — RIP-seq plus knockdown with cellular phenotype; association with splicing factors shown by single method; single lab\",\n      \"pmids\": [\"31088452\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MOV10 interacts with MERS-CoV nucleocapsid (N) protein (confirmed by endogenous Co-IP), colocalizes with N protein in cytoplasmic aggregates, and sequesters viral RNA in these complexes (RNA-IP). MOV10 silencing increases both N protein levels and virus titer. The helicase activity of MOV10 is required for its antiviral effect against MERS-CoV, shown using CRISPR KO cells expressing WT vs. helicase-dead MOV10. MOV10-N interaction is conserved across human CoVs including SARS-CoV-2.\",\n      \"method\": \"Co-IP (endogenous), RNA immunoprecipitation, CRISPR KO cell lines, WT vs. helicase-dead mutant complementation, viral titer assay\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — endogenous Co-IP plus RNA-IP plus CRISPR KO plus mutagenesis; single lab, multiple methods\",\n      \"pmids\": [\"34517762\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"MOV10 and APOBEC3G localization to P-bodies is NOT required for virion incorporation or antiviral activity against HIV-1. A helicase V mutant of MOV10 has significantly reduced P-body localization but still efficiently inhibits viral infectivity via virion incorporation. CRISPR/DDX6-knockdown-disrupted P-bodies confirmed MOV10 antiviral activity without P-body localization. AGO2-mediated RNA-induced silencing is required for MOV10's ability to reduce Gag expression upon overexpression, but NOT for virion incorporation or infectivity effects.\",\n      \"method\": \"P-body disruption by DDX6 knockdown, helicase V mutant analysis, sucrose gradient sedimentation, AGO2 depletion, infectivity assay\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple dissection approaches (mutagenesis, P-body disruption, AGO2 depletion) with specific functional readouts; single lab\",\n      \"pmids\": [\"23926332\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"MOV10 inhibits PRRSV replication by interacting with the viral nucleocapsid (N) protein in the cytoplasm and retaining N protein in the cytoplasm, preventing its nuclear import. MOV10 does not affect virus attachment or internalization.\",\n      \"method\": \"Stable MOV10 overexpression, Co-IP, immunofluorescence co-localization, subcellular fractionation, adsorption assay\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Co-IP plus co-localization plus overexpression functional assay; single lab, limited mechanistic depth\",\n      \"pmids\": [\"30172377\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MOV10 forms a complex with UPF1 in mouse testis and primarily binds 3' UTRs of somatically expressed transcripts. Loss of MOV10 in mice results in an altered testis transcriptome and increased LINE-1 retrotransposition in somatic and reproductive tissues in a dosage-dependent manner. MOV10 deficiency reduces reproductive fitness over successive generations.\",\n      \"method\": \"MOV10 KO mouse (conditional), LINE-1 reporter transgene, RNA-seq, biochemical Co-IP for UPF1 complex\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo mouse KO with LINE-1 reporter transgene plus biochemical complex validation; single lab\",\n      \"pmids\": [\"37126510\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"MOV10 inhibits Vif-mediated degradation of APOBEC3G by interfering with assembly of the Vif-CBF-β-Cullin5-ElonginB-ElonginC E3 ubiquitin ligase complex. The DEAG-box of MOV10 is required for this inhibition.\",\n      \"method\": \"Co-IP for E3 ligase complex components, western blot for A3G levels, DEAG-box mutagenesis, proteasome assay\",\n      \"journal\": \"Retrovirology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Co-IP with mutagenesis for complex inhibition; single lab, mechanism partially characterized\",\n      \"pmids\": [\"29258557\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"MOV10 sequesters influenza A virus RNP in the cytoplasm by interacting with viral NP, and this leads to degradation of viral vRNA. P-body integrity is required for MOV10's antiviral activity. Viral NS1 protein antagonizes MOV10 by interfering with MOV10-NP interaction and promoting MOV10 degradation via the lysosomal pathway.\",\n      \"method\": \"Co-IP, RNA degradation assay, P-body disruption (DDX6 knockdown), NS1 co-expression, lysosome inhibitor treatment, viral RNA quantification\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus functional P-body disruption plus pharmacological lysosome inhibition; single lab\",\n      \"pmids\": [\"30617221\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Knockdown of maternal Mov10 in Xenopus laevis embryos causes defects in gastrulation, notochord and paraxial mesoderm development, and failure to neurulate. Degradation of the miR-427 target mRNA cyclin A1 (maternal-to-zygotic transition event) is delayed in Mov10 knockdowns. Zygotic Mov10 knockdown impairs head, eye, and brain development.\",\n      \"method\": \"Translation-blocking morpholino knockdown in Xenopus, RNA-seq, developmental phenotype analysis, cyclin A1 mRNA stability assay\",\n      \"journal\": \"Developmental dynamics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — morpholino knockdown with specific developmental phenotype plus RNA-seq and mRNA stability readout; single lab\",\n      \"pmids\": [\"29266590\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MOV10 regulates dendritic arborization and NUMA1 mRNA translation in hippocampal neurons. In brain-specific Mov10 KO mice, NUMA1 expression is decreased. Restoration of NUMA1 expression or knockdown of HAUS rescued abnormal dendritic phenotypes in Mov10 KO hippocampal neurons. Enhanced fear memory is observed in Mov10 KO mice.\",\n      \"method\": \"Brain-specific MOV10 KO mouse, MOV10 CLIP-seq (NUMA1 identified as target), rescue experiments with NUMA1 overexpression and HAUS knockdown, dendritic morphometry\",\n      \"journal\": \"BMC biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO mouse plus CLIP evidence plus molecular rescue experiments; single lab\",\n      \"pmids\": [\"39915816\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The extended motif II (residues 563-675) and the C-terminal domain (residues 907-1003) of MOV10 cooperate for maximal inhibition of LINE-1 retrotransposition. The extended motif II mediates MOV10-LINE-1 RNA/RNP interaction and is dominant for anti-LINE-1 activity. The C-terminal domain mediates MOV10's association with G3BP1 and formation of cytoplasmic granules, which promotes maximal inhibition.\",\n      \"method\": \"Domain deletion/truncation mutagenesis, retrotransposition assay, Co-IP for G3BP1, immunofluorescence for granule formation\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic domain mutagenesis with multiple functional readouts; single lab\",\n      \"pmids\": [\"40408535\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The N-terminal domain of MOV10 is functionally distinct from the CH domain of UPF1: it impacts catalytic helicase activity differently and mediates different protein-protein interactions. MOV10 engages the NMD factor UPF2 via its N-terminal regulatory domain, but at a different region than UPF1's CH domain binds UPF2. The MOV10 N-terminal domain dictates its localization to cytoplasmic RNA condensates (P-bodies and stress granules), distinct from UPF1 whose localization is RNA-driven.\",\n      \"method\": \"In vitro biochemical assays, domain mutagenesis, protein-protein interaction mapping, localization studies\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical reconstitution with domain mutagenesis; single lab, single paper\",\n      \"pmids\": [\"40570961\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"MOV10 drives sequestration of LINE-1 ribonucleoprotein complexes into cytoplasmic aggregates, restricting retrotransposition. Combined overexpression of L1 ORF1p and MOV10 is sufficient to create L1 RNP aggregates. In Dicer KO mESCs, MOV10 is upregulated due to loss of direct miRNA regulation, and this elevated MOV10 drives L1 aggregate formation.\",\n      \"method\": \"Dicer KO mESCs, co-overexpression experiments, immunofluorescence, retrotransposition assay, miRNA regulation of Mov10 3'UTR\",\n      \"journal\": \"EMBO reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — KO cells plus co-overexpression rescue plus functional retrotransposition readout; single lab\",\n      \"pmids\": [\"35856394\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"MOV10 is ISGylated (modified by ISG15), and ISGylated MOV10 enhances IFN-β production/secretion. The deubiquitylase USP24 specifically de-ISGylates MOV10 to negatively regulate the innate immune IFN-I response. USP24 depletion increases ISG15 conjugate accumulation and was identified as a novel ISG15 cross-reactive DUB by activity-based protein profiling.\",\n      \"method\": \"Activity-based protein profiling (ABPP), in vitro USP24 ISG15-substrate cleavage assay, proteomics (total proteome/GG-peptidome/ISG15 interactome), USP24 depletion, IFN-β reporter assay\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — multi-omic identification plus in vitro and cell-based validation; preprint, single lab, not yet peer-reviewed\",\n      \"pmids\": [\"bio_10.1101_2024.09.06.611391\"],\n      \"is_preprint\": true\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"The gb110 gene (MOV10) has a 133-bp intronic enhancer that activates expression ~50-100 fold in undifferentiated F9 embryonal carcinoma cells. This enhancer is inactive in differentiated cells, mediating differentiation-specific downregulation. Four protein-binding sites were identified, including GC/GT-box motifs bound cooperatively by Sp1-related proteins; one GT-box-binding protein is present only in undifferentiated F9 cells.\",\n      \"method\": \"Transient chloramphenicol acetyltransferase (CAT) reporter assay, DNase I footprinting, gel mobility shift assay, mutational analysis of binding sites\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — functional reporter assay with systematic mutational analysis defining cis-regulatory elements; single lab\",\n      \"pmids\": [\"8065313\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MOV10 is an ATP-dependent superfamily-1 RNA helicase that unwinds RNA with 5'-to-3' directionality, associates with RISC components (AGO2) and translational regulators (FMRP, UPF1), and acts as a broad-spectrum antiviral and antiretrotransposon factor: it suppresses LINE-1/Alu/SVA retrotransposons and diverse RNA/DNA viruses through mechanisms including viral RNA degradation (recruiting DCP2 for decapping via liquid-liquid phase separation), helicase-dependent RNA clearance to facilitate UPF1-mediated mRNA decay, and helicase-independent blockade of viral nucleoprotein nuclear import; in neurons it undergoes activity-dependent proteasomal degradation downstream of NMDA-receptor stimulation to relieve translational silencing of synaptic mRNAs, and its activity is further regulated by phosphorylation at S970 (restricting helicase activity and enabling AGO2-mediated mRNA degradation) and by CRL4-DCAF12-mediated ubiquitination/proteasomal degradation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MOV10 is an ATP-dependent superfamily-1 RNA helicase that translocates 5'-to-3' along RNA and acts broadly in post-transcriptional RNA regulation, retroelement restriction, and antiviral defense [#0, #3]. As an RNA clearance factor it binds 3' UTRs upstream of structured regions and partners with UPF1 to promote decay of co-bound transcripts [#0], and in the brain it forms an FMRP- and AGO2-containing inhibitory complex on synaptic mRNAs whose balance is set by FMRP's RGG box and MOV10's N-terminal domain [#2, #21, #23]. MOV10 is a potent suppressor of LINE-1, Alu, and SVA retrotransposons, acting through its helicase domain by associating with the L1 ribonucleoprotein and ORF1p to reduce L1 RNA, sequestering L1 RNP into cytoplasmic/stress-granule aggregates, recruiting the decapping enzyme DCP2 in a phase-separating complex to degrade L1 RNA, and cooperating with RNASEH2 to resolve L1 RNA-DNA hybrids [#3, #4, #24, #14, #39]. It restricts a wide range of viruses by both helicase-dependent and helicase-independent routes: it is packaged into HIV-1 virions via the nucleocapsid and blocks replication post-entry [#5, #6, #12], degrades influenza vRNA and retains viral nucleoprotein in the cytoplasm to block nuclear import [#8, #34], and similarly targets the nucleoproteins of bunyaviruses, coronaviruses, and other RNA viruses, in some cases by boosting IRF3/IKK\\u03b5-driven type I interferon induction [#22, #29, #10]. MOV10 activity is regulated by S970 phosphorylation, which restricts helicase-mediated G-quadruplex unwinding and switches transcripts toward AGO2-mediated degradation [#25], and by CRL4-DCAF12-directed ubiquitination and proteasomal turnover [#19]. In neurons, MOV10 undergoes NMDA-receptor-driven, proteasome-dependent degradation to relieve translational silencing of synaptic mRNAs [#1], and it is required for neurite outgrowth and dendritic arborization through regulation of cytoskeletal and NUMA1 mRNAs [#20, #36]. MOV10 is essential for development, with knockout causing embryonic lethality in mice and gastrulation/neurulation defects in Xenopus, and it supports reproductive fitness by restraining LINE-1 in the germline [#20, #35, #32].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Before any protein function was known, the question was how MOV10 expression is controlled; this established differentiation-coupled transcriptional regulation of the gene.\",\n      \"evidence\": \"CAT reporter assays, DNase I footprinting, and mutational analysis of a 133-bp intronic enhancer in F9 embryonal carcinoma cells\",\n      \"pmids\": [\"8065313\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not address the protein's molecular function\", \"Identity of the undifferentiated-cell-specific GT-box factor unresolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"The first functional clue placed MOV10 in RNA-directed processes; its requirement for HDV replication but not HDAg translation implicated it in RNA-templated transcription rather than translation.\",\n      \"evidence\": \"HDAg-interaction screen with MOV10 knockdown and separate HDV replication and translation readouts\",\n      \"pmids\": [\"18552826\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Helicase activity not directly tested here\", \"Mechanism of action on HDV RNA undefined\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Two independent contexts established MOV10 as a regulated RNA-handling factor: activity-dependent proteasomal degradation at synapses controlling local translation, and a contested telomerase association.\",\n      \"evidence\": \"Synaptic translational trap, polysome fractionation, proteasome inhibition and NMDAR stimulation in neurons; separately, co-purification of telomerase activity with anti-MOV10 IP and telomere DNA binding\",\n      \"pmids\": [\"20064393\", \"19665004\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"The telomerase association (idx 27) is Low-confidence, single-lab, and not replicated\", \"Direct helicase action on the synaptic target mRNAs not shown in 2009\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"MOV10 was defined as a broad retroviral restriction factor and a nuclear chromatin-associated regulator, establishing its antiviral identity and a PRC1-linked epigenetic role.\",\n      \"evidence\": \"Reciprocal overexpression/knockdown HIV-1 infectivity assays, virion incorporation, and domain mapping; plus chromatin fractionation, PRC1 co-IP and ChIP at the INK4a locus\",\n      \"pmids\": [\"20215113\", \"20668078\", \"20543829\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"N-terminal vs helicase contributions to HIV restriction only partly resolved\", \"Mechanism of PRC1 recruitment to chromatin undefined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"MOV10 was established as a helicase-dependent restrictor of endogenous retroelements and its interface with the RISC/APOBEC3G machinery was mapped, distinguishing antiretroelement from antiretrovirus activity.\",\n      \"evidence\": \"Retrotransposition assays across L1/Alu/SVA with helicase mutants and L1 RNP co-IP; RNAi specificity for endogenous elements; APOBEC3G domain-mapped competition for AGO2 binding via 7SL RNA\",\n      \"pmids\": [\"23093941\", \"22727223\", \"22791714\", \"22105071\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Exact step in retrotransposition blocked not fully defined\", \"Whether RISC association is required for antiretroelement activity unresolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Mechanistic dissection showed MOV10 suppresses L1 by helicase-dependent reduction of L1 RNA, and clarified that P-body localization is dispensable for HIV restriction.\",\n      \"evidence\": \"Helicase-motif mutagenesis with L1 RNA quantification and ORF1 co-IP; P-body disruption by DDX6 knockdown and helicase-V mutant analysis with HIV infectivity readouts\",\n      \"pmids\": [\"23754279\", \"23926332\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Nuclease/effector that degrades L1 RNA not identified in 2013\", \"How helicase translocation triggers RNA degradation unclear\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Biochemical reconstitution and CLIP defined MOV10's directional helicase activity and its role as an RNA clearance factor for UPF1-mediated decay, and revealed a dual relationship with the miRNA/FMRP machinery.\",\n      \"evidence\": \"In vitro 5'-to-3' unwinding with helicase mutants, PAR-CLIP, UPF1 co-IP and mRNA half-life measurements; reciprocal FMRP co-IP, iCLIP and reporter assays\",\n      \"pmids\": [\"24726324\", \"25464849\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How MOV10 both promotes and antagonizes AGO2 on different transcripts not mechanistically resolved\", \"Determinants of UPF1 vs FMRP coupling unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Helicase-independent antiviral modes were established: cytoplasmic retention of influenza nucleoprotein blocking nuclear import, and IFN-pathway amplification via IRF3/IKK\\u03b5 independent of RIG-I/MAVS.\",\n      \"evidence\": \"Knockdown/KO with minigenome, importin-\\u03b1 binding and fractionation assays for influenza NP; IFN reporter and kinase KO experiments for broad RNA-virus restriction\",\n      \"pmids\": [\"26842467\", \"27016603\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How MOV10 activates IKK\\u03b5 specifically is undefined\", \"Connection between NP sequestration and IFN induction unclear\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"A nuclear partner for L1 restriction was identified, linking MOV10 to RNASEH2-dependent resolution of L1 RNA-DNA hybrids.\",\n      \"evidence\": \"Proteomic co-IP, nuclear co-localization, shRNA knockdown, retrotransposition and RNA-DNA hybrid detection\",\n      \"pmids\": [\"29315404\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Order of MOV10 and RNASEH2 action on hybrids not established\", \"Whether helicase activity feeds hybrid formation unclear\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"In vivo and biochemical work established MOV10's essential developmental and neuronal roles, refined its synaptic FMRP/AGO2 switch, and extended antiviral targeting to HBV.\",\n      \"evidence\": \"Mov10 KO/heterozygote mice (embryonic lethality, RIP-seq, neurite outgrowth), synaptoneurosome co-IP/polysome NMDAR stimulation, N-terminus/RGG-box G-quadruplex mapping, and HBV helicase-mutant RNA-binding assays\",\n      \"pmids\": [\"28662698\", \"31291981\", \"31740951\", \"31722967\", \"31252377\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vivo function of helicase activity in neurons not isolated\", \"Kinase responsible for the FMRP/MOV10 phospho-switch unidentified\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"MOV10 was shown to disable viral nucleoprotein assembly across diverse viruses and to relocalize to viral replication sites, defining a recurring nucleoprotein-targeting antiviral strategy.\",\n      \"evidence\": \"Mass spectrometry, N-polymerization/RNA-binding and minigenome assays with in vivo infection for bunyaviruses; CRISPR KO and mutagenesis for HCV with lipid-droplet relocalization imaging\",\n      \"pmids\": [\"33284835\", \"32496609\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Why MOV10 is proviral for HCV but antiviral for most viruses unresolved\", \"Structural basis of N-arm binding limited to one virus family\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"MOV10 turnover was placed under CRL4-DCAF12 control with a germline phenotype, and helicase-dependent coronavirus restriction plus a NUMA1-dependent dendritic role were established.\",\n      \"evidence\": \"CRL4-DCAF12 co-purification with DCAF12 KO mice; CRISPR KO/helicase-dead complementation for MERS-CoV with RNA-IP; brain-specific Mov10 KO with NUMA1/HAUS rescue (idx 36 reported 2025)\",\n      \"pmids\": [\"34065512\", \"34517762\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signals controlling DCAF12-mediated MOV10 degradation unknown\", \"Link between MOV10 levels and meiotic progression not mechanistic\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The L1-clearance effector and a regulatory phospho-switch were defined: MOV10 recruits DCP2 to decap L1 RNA in a phase-separating complex, and S970 phosphorylation restricts helicase activity to redirect transcripts toward AGO2 degradation.\",\n      \"evidence\": \"Co-IP, phase-separation and in vitro decapping assays with retrotransposition readout; mass-spectrometry-identified S970 with G-quadruplex unwinding assays, RNA-seq and AGO2 knockdown\",\n      \"pmids\": [\"37437058\", \"36871759\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Kinase phosphorylating S970 not identified\", \"How phase separation couples to decapping efficiency unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Domain-level dissection separated MOV10's helicase/RNP-binding and granule-forming functions and distinguished its N-terminal regulatory domain from the UPF1 CH domain in NMD coupling.\",\n      \"evidence\": \"Domain truncation/mutagenesis with retrotransposition and G3BP1 co-IP for L1 restriction; in vitro biochemistry and interaction mapping with UPF2/UPF1\",\n      \"pmids\": [\"40408535\", \"40570961\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of MOV10-UPF2 engagement not solved\", \"How granule formation enhances catalytic restriction unclear\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MOV10 selects between its opposing outputs \\u2014 protecting versus degrading bound mRNAs, restricting versus assisting viruses, and acting via helicase-dependent versus helicase-independent routes \\u2014 remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unifying model for substrate/context selection\", \"Upstream kinases for S970 and the synaptic FMRP switch unidentified\", \"Structural mechanism of nucleoprotein sequestration vs RNA unwinding undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 2, 4, 16, 26]},\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [0, 24, 26]},\n      {\"term_id\": \"GO:0140657\", \"supporting_discovery_ids\": [0, 26]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 13, 33]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [27]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [7, 14, 28]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [8, 31, 34]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [6, 15, 18, 34]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 2, 24, 25]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [5, 8, 10, 22, 29]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [5, 16, 18, 29]},\n      {\"term_id\": \"R-HSA-112316\", \"supporting_discovery_ids\": [1, 20, 21, 36]}\n    ],\n    \"complexes\": [\n      \"RISC (with AGO2)\",\n      \"MOV10-FMRP-AGO2 inhibitory complex\",\n      \"MOV10-UPF1 complex\",\n      \"PRC1\"\n    ],\n    \"partners\": [\n      \"UPF1\",\n      \"FMRP\",\n      \"AGO2\",\n      \"DCP2\",\n      \"RNASEH2\",\n      \"G3BP1\",\n      \"UPF2\",\n      \"APOBEC3G\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}