Affinage

LSM14A

Protein LSM14 homolog A · UniProt Q8ND56

Length
463 aa
Mass
50.5 kDa
Annotated
2026-06-10
20 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LSM14A (RAP55) is a cytoplasmic RNA-binding protein that controls mRNA fate and serves as a viral nucleic-acid sensor in innate immunity (PMID:16484376, PMID:22745163). In resting cells it nucleates P-bodies and relocates to stress granules under arsenite stress, with its FDF and two RGG-rich domains directing P-body targeting and the second RGG domain driving stress-granule localization; its loss eliminates P-bodies, placing it upstream of 5'-decapping in mRNA turnover (PMID:16484376). Through its N-terminal LSm domain it directly represses translation, acting on bound mRNAs in cooperation with the DEAD-box helicase Xp54/DDX6 (PMID:17074753). P-body targeting is governed by PRMT1-mediated asymmetric dimethylation of multiple arginine residues, which is selectively required for LSM14A recruitment while other P-body components remain (PMID:22614839). Upon viral infection, LSM14A binds both viral RNA and DNA and translocates to peroxisomes to drive early IRF3 activation and IFN-β induction via RIG-I-VISA for RNA viruses or MITA/STING for DNA viruses (PMID:22745163); in dendritic cells it additionally supports MITA/STING expression by promoting nuclear mRNA precursor processing (PMID:27183626). This antiviral function is antagonized by viral proteins including influenza NS1 and SFTSV NSs, which bind LSM14A to disrupt granule formation and block IRF3 phosphorylation (PMID:22973032, PMID:34244294). Beyond RNA regulation and immunity, LSM14A stabilizes DDX5 to modulate CDK4/p21 and promote cell-cycle progression (PMID:39040050) and binds tubulin to support mitotic spindle stability (PMID:26339800).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2006 High

    Established LSM14A as a core P-body and stress-granule protein and mapped the domains that target it to each, defining it as a structural organizer of mRNA-regulatory granules upstream of decapping.

    Evidence siRNA knockdown, GFP-tagged domain-deletion mutants, and colocalization with DCP1a/Ge-1 in stress assays

    PMID:16484376

    Open questions at the time
    • Did not define the mRNAs regulated
    • Mechanistic link between granule loss and decapping not resolved
  2. 2006 High

    Showed the protein directly represses translation through its LSm domain in cooperation with the DEAD-box helicase Xp54, providing the biochemical basis for its repressive function in mRNPs.

    Evidence Affinity purification, in vitro translation and oocyte tethering assays, domain mapping, and Co-IP in Xenopus

    PMID:17074753

    Open questions at the time
    • Human ortholog repression not reconstituted in this study
    • Mechanism of Xp54 cooperation at molecular level unresolved
  3. 2012 High

    Identified PRMT1 as the writer of asymmetric arginine dimethylation that is specifically required for LSM14A P-body targeting, revealing post-translational control of its granule localization.

    Evidence PRMT1 siRNA knockdown, mass-spec identification of dimethylarginine sites, and Co-IP

    PMID:22614839

    Open questions at the time
    • Functional consequence of methylation on translation repression untested
    • Role of PRMT5 left unclear
  4. 2012 High

    Recast LSM14A as a viral RNA/DNA sensor that initiates early IFN-β induction by translocating to peroxisomes and signaling through RIG-I-VISA or MITA, linking an mRNA-regulatory protein to innate immune sensing.

    Evidence RNA/DNA binding assays, siRNA knockdown, IFN-β reporter assays, viral infection, fractionation, and genetic epistasis

    PMID:22745163

    Open questions at the time
    • How sensing connects mechanistically to RIG-I/MITA at peroxisomes unresolved
    • Relationship to its P-body function unclear
  5. 2012 High

    Demonstrated that influenza NS1 targets LSM14A to disrupt granules and suppress its antiviral activity, establishing LSM14A as a restriction factor counteracted by viruses.

    Evidence Co-IP, colocalization, NS1 site-directed mutagenesis, and knockdown/overexpression viral replication assays

    PMID:22973032

    Open questions at the time
    • Direct link between granule disruption and IFN suppression not dissected
  6. 2015 Medium

    Extended LSM14A function beyond mRNA control to mitosis, showing it binds tubulin and is required for spindle stability.

    Evidence GFP localization, siRNA depletion with mitotic-arrest phenotype, and in vitro tubulin binding in HeLa cells

    PMID:26339800

    Open questions at the time
    • Single lab, limited orthogonal validation
    • How an RNA-binding granule protein stabilizes the spindle mechanistically unknown
  7. 2016 High

    Revealed a cell-type-specific role in which LSM14A sustains MITA/STING protein by supporting its nuclear mRNA precursor processing in dendritic cells, distinguishing this from its cytoplasmic sensing role.

    Evidence Lsm14a knockout mice, cell-type-specific analysis, mRNA processing assays, and IFN induction after multiple viral infections

    PMID:27183626

    Open questions at the time
    • Mechanism of nuclear mRNA processing by a cytoplasmic protein unresolved
    • Why effect is dendritic-cell specific unexplained
  8. 2021 Medium

    Identified a second viral antagonist, SFTSV NSs, that binds LSM14A via an LRRD motif to block IRF3 phosphorylation/dimerization, reinforcing LSM14A as a node viruses target to suppress IFN.

    Evidence Co-IP, colocalization, proteomic screening, motif mutagenesis, and IRF3 phosphorylation/dimerization assays

    PMID:34244294

    Open questions at the time
    • Single lab
    • Whether NSs blocks RNA binding versus signaling step not fully separated
  9. 2024 Medium

    Linked LSM14A to cell-cycle control by showing it stabilizes DDX5 to regulate CDK4/p21 and promote glioblastoma proliferation, with its own expression set by METTL1-dependent m7G methylation.

    Evidence Co-IP, mass spec, protein half-life and MeRIP assays, proliferation/migration readouts, and xenograft model

    PMID:39040050

    Open questions at the time
    • Single lab
    • Mechanism by which LSM14A stabilizes DDX5 unresolved
    • Generalizability beyond glioblastoma untested
  10. 2026 Medium

    Challenged the granule/peroxisome model of LSM14A antiviral signaling by showing its immune amplification depends on a distinct cohort of interactors assembling outside P-bodies and peroxisomes.

    Evidence Unbiased interactomic analysis after Sendai virus infection with functional interrogation of interactors (preprint)

    PMID:42182482

    Open questions at the time
    • Preprint, not peer-reviewed, single lab
    • Identity and architecture of the signaling complex not fully defined
  11. 2025 Medium

    Tested the in vivo requirement of LSM14A in germ cells and found it dispensable for spermatogenesis and male fertility, bounding its essential roles to other tissues/contexts.

    Evidence Germ-cell-specific conditional knockout mice with histology, sperm analysis, and P-body marker immunofluorescence

    PMID:41237998

    Open questions at the time
    • Negative result; possible redundancy with paralogs not addressed
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular composition and architecture of the non-canonical signaling complex that drives LSM14A antiviral amplification, and how it integrates with its granule and translational-repression activities, remain undefined.
  • No structural model of the antiviral complex
  • Connection between mRNA-repression, sensing, and mitotic functions unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0003677 DNA binding 1 GO:0008092 cytoskeletal protein binding 1 GO:0045182 translation regulator activity 1 GO:0140299 molecular sensor activity 1
Localization
GO:0005829 cytosol 3 GO:0005777 peroxisome 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-1640170 Cell Cycle 2 R-HSA-8953854 Metabolism of RNA 2
Partners
DDX5DDX6MITAPRMT1RIG-IVISA
Complex memberships
P-bodystress granule

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 RAP55 (LSM14A) localizes to P-bodies in resting cells and to stress granules after arsenite-induced stress. The FDF motif and two RGG-rich domains are necessary and sufficient for P-body targeting, while the second RGG domain is necessary and sufficient for stress granule localization. siRNA-mediated knockdown of RAP55 results in loss of P-bodies, placing RAP55 upstream of the 5'-decapping step in mRNA degradation. siRNA knockdown, GFP-tagged domain deletion mutants, immunofluorescence colocalization with DCP1a and Ge-1, arsenite-stress assay RNA (New York, N.Y.) High 16484376
2006 Xenopus RAP55 (xRAP55/LSM14A ortholog) is a component of maternal mRNPs that directly represses translation in vitro and in oocytes when tethered to a reporter mRNA. The N-terminal LSm domain is required for P-body localization and translational repression. xRAP55 cooperates with the DEAD-box protein Xp54 to repress translation, and associates with PRMT1. Affinity purification of xRAP55 complexes from Xenopus oocytes, in vitro translation assay with recombinant protein, tethering assay in oocytes, domain deletion analysis, co-immunoprecipitation The Journal of biological chemistry High 17074753
2012 LSM14A binds to synthetic or viral RNA and DNA, mediates IRF3 activation and IFN-β induction, and is essential for early-phase IFN-β induction after RNA or DNA virus infection. LSM14A-mediated IFN-β induction requires RIG-I-VISA (for RNA viruses) or MITA (for DNA viruses). Viral infection causes translocation of LSM14A to peroxisomes, where RIG-I, VISA, and MITA are located. RNA/DNA binding assays, siRNA knockdown of LSM14A, IFN-β reporter assays, viral infection experiments, subcellular fractionation/immunofluorescence showing peroxisomal translocation, epistasis with RIG-I/VISA/MITA knockdowns Proceedings of the National Academy of Sciences of the United States of America High 22745163
2012 PRMT1 asymmetrically dimethylates multiple arginine residues of RAP55A (LSM14A). Knockdown of PRMT1 impairs localization of RAP55A to P-bodies while other P-body components are retained, establishing PRMT1 as a writer required for RAP55A P-body targeting. RAP55A overexpression induces formation of large mRNP granules containing both P-body and stress granule components. siRNA knockdown of PRMT1, immunofluorescence, mass spectrometry identification of asymmetric dimethylarginine on RAP55A, co-immunoprecipitation of PRMT1/PRMT5 with RAP55A RNA biology High 22614839
2012 Influenza A NS1 protein interacts with RAP55 (LSM14A) via its RNA-binding (R38, K41) and PKR-interaction (I123, M124, K126, N127) sites. NS1 interaction with RAP55 inhibits RAP55 expression and disrupts P-body/stress granule formation. Overexpression of RAP55 suppresses influenza virus replication, while dominant-negative RAP55 blocks NS1 colocalization to P-bodies. Co-immunoprecipitation, colocalization assays, siRNA knockdown of RAP55, site-directed mutagenesis of NS1, overexpression and dominant-negative mutant analysis Journal of virology High 22973032
2016 LSM14A deficiency specifically downregulates MITA/STING protein level in dendritic cells (but not in macrophages or fibroblasts) by impairing nuclear mRNA precursor processing of MITA/STING, thereby impairing antiviral innate and adaptive immune responses in a cell-type-specific manner. LSm14a-deficient (knockout) mice, cell-type-specific analysis, nuclear mRNA precursor processing assays, IFN induction assays after HSV-1, MHV-68, VSV infection Journal of immunology (Baltimore, Md. : 1950) High 27183626
2021 SFTSV nonstructural protein NSs interacts with LSM14A via a newly identified LRRD motif on NSs. This interaction inhibits downstream IRF3 phosphorylation and dimerization, suppressing IFN-β induction. Viral RNA is bound to the LSm14A-NSs protein complex during the interaction. Co-immunoprecipitation, colocalization, siRNA knockdown of NSs, proteomic screening, IRF3 phosphorylation/dimerization assays, viral replication assays Journal of immunology (Baltimore, Md. : 1950) Medium 34244294
2015 RAP55/LSM14A localizes to the mitotic spindle during mitosis in HeLa cells. Depletion of RAP55/LSM14A destabilizes spindle assembly and arrests cells in mitosis. In vitro binding assay demonstrates that RAP55/LSM14A binds directly to tubulin. GFP-tagged protein expression in HeLa cells, immunofluorescence during mitosis, siRNA depletion, in vitro tubulin-binding assay Acta biochimica Polonica Medium 26339800
2024 LSM14A stabilizes DDX5 protein in the cytoplasm during the G1/S phase, regulating CDK4 and P21 levels to promote glioblastoma cell proliferation and migration. METTL1 modulates LSM14A expression via mRNA m7G methylation. LSM14A interacts with DDX5 as identified by mass spectrometry and co-immunoprecipitation. Co-immunoprecipitation, mass spectrometry, protein half-life assay, MeRIP analysis, CCK8/EdU/colony formation/transwell assays, in vivo xenograft model iScience Medium 39040050
2026 LSM14A's antiviral innate immune function does not require its localization to P-bodies or peroxisomes. Instead, an unbiased interactomic analysis after Sendai virus infection revealed a distinct cohort of LSM14A-associated proteins assembling outside P-bodies and peroxisomes that are essential for LSM14A-dependent amplification of antiviral signaling. Interactomic/proteomic analysis (systems-level), functional interrogation of interactors, localization experiments, Sendai virus infection model bioRxivpreprint Medium 42182482
2025 LSM14A is expressed in mouse testis germ cells from spermatogonia to elongating spermatids and localizes to the cytoplasm. Germ cell-specific conditional knockout of Lsm14a in mice did not affect spermatogenesis, sperm morphology, motility, or male fertility, nor did it significantly affect P-body formation in testes. Conditional knockout mouse model, histological examination, sperm morphology/motility analysis, immunofluorescence for P-body markers Cells & development Medium 41237998

Source papers

Stage 0 corpus · 20 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 RNA-associated protein 55 (RAP55) localizes to mRNA processing bodies and stress granules. RNA (New York, N.Y.) 147 16484376
2012 LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection. Proceedings of the National Academy of Sciences of the United States of America 130 22745163
2006 RAP55, a cytoplasmic mRNP component, represses translation in Xenopus oocytes. The Journal of biological chemistry 98 17074753
2012 The NS1 protein of influenza A virus interacts with cellular processing bodies and stress granules through RNA-associated protein 55 (RAP55) during virus infection. Journal of virology 59 22973032
2012 PRMT1 is required for RAP55 to localize to processing bodies. RNA biology 44 22614839
2008 RAP55: insights into an evolutionarily conserved protein family. The international journal of biochemistry & cell biology 42 18723115
2016 LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner. Journal of immunology (Baltimore, Md. : 1950) 37 27183626
2021 Nonstructural Protein NSs Hampers Cellular Antiviral Response through LSm14A during Severe Fever with Thrombocytopenia Syndrome Virus Infection. Journal of immunology (Baltimore, Md. : 1950) 19 34244294
2014 LSM14A inhibits porcine reproductive and respiratory syndrome virus (PRRSV) replication by activating IFN-β signaling pathway in Marc-145. Molecular and cellular biochemistry 18 25408553
2019 Molecular characterization and expression of the teleost cytosolic DNA sensor genes cGAS, LSm14A, DHX9, and DHX36 in Japanese medaka, Oryzias latipes. Developmental and comparative immunology 15 31141705
2024 METTL1-modulated LSM14A facilitates proliferation and migration in glioblastoma via the stabilization of DDX5. iScience 12 39040050
2015 Localization and role of RAP55/LSM14 in HeLa cells: a new finding on the mitotic spindle assembly. Acta biochimica Polonica 12 26339800
2022 A novel fusion variant LSM14A::NR4A3 in extraskeletal myxoid chondrosarcoma. Genes, chromosomes & cancer 10 35932215
2015 The Scd6/Lsm14 protein xRAPB has properties different from RAP55 in selecting mRNA for early translation or intracellular distribution in Xenopus oocytes. Biochimica et biophysica acta 10 26455898
2017 Functional characterization of duck LSm14A in IFN-β induction. Developmental and comparative immunology 9 28666650
2013 Functional characterization of porcine LSm14A in IFN-β induction. Veterinary immunology and immunopathology 8 23871214
2019 Transcriptional responses of LSm14A after infection of blue eggshell layers with Newcastle disease viruses. The Journal of veterinary medical science 4 31534060
2026 Silencer-regulated circLSM14A inhibits autophagy of pulmonary artery smooth muscle cells through parental protein LSM14A. Free radical biology & medicine 0 41679563
2026 The enteroviral protease target LSM14A operates outside of P-bodies to augment antiviral innate immunity. bioRxiv : the preprint server for biology 0 42182482
2025 LSM14A, an LSM family protein, is dispensable for spermatogenesis and male fertility in mice. Cells & development 0 41237998

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