{"gene":"FTSJ3","run_date":"2026-06-09T23:54:44","timeline":{"discoveries":[{"year":2019,"finding":"FTSJ3 is a 2'-O-methyltransferase (2'O-MTase) that forms a DICER-independent complex with TRBP (TAR RNA-binding protein). This complex is recruited to HIV-1 RNA via TRBP, where FTSJ3 installs 2'-O-methylations at specific residues on the viral genome. Hypomethylated HIV-1 produced in FTSJ3 knockdown cells triggers MDA5-mediated type I interferon (IFN-α and IFN-β) responses in human dendritic cells, demonstrating that FTSJ3-mediated 2'-O-methylation shields HIV-1 RNA from innate immune sensing.","method":"TRBP complex purification and mass spectrometry; in vitro and ex vivo 2'O-MTase activity assays; RiboMethSeq mapping of methylation sites; shRNA knockdown; IFN induction assays in human dendritic cells","journal":"Nature","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (biochemical purification, in vitro enzymatic assay, RiboMethSeq, KD with functional IFN readout) in a single rigorous study","pmids":["30626973"],"is_preprint":false},{"year":2011,"finding":"FTSJ3 physically associates with human NIP7 (a ribosome biogenesis factor) and localizes to the nucleolus. Conditional knockdown of FTSJ3 causes accumulation of the 34S pre-rRNA (spanning site A' to site 2b), indicating that FTSJ3 is required for efficient processing at sites A0, 1, and 2 in the pathway leading to 18S rRNA maturation, implicating FTSJ3 in 40S ribosomal subunit biogenesis.","method":"Yeast two-hybrid; coimmunoprecipitation; colocalization (immunofluorescence); conditional shRNA knockdown; Northern blot analysis of pre-rRNA processing intermediates","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, colocalization, KD with specific pre-rRNA processing phenotype, multiple orthogonal methods in one study","pmids":["22195017"],"is_preprint":false},{"year":2012,"finding":"FLAG-tagged FTSJ3 coimmunoprecipitates both small (RPS) and large (RPL) ribosomal proteins as well as ribosome synthesis factors in preribosomal complexes. The C-terminal Spb1_C domain of FTSJ3 mediates its interaction with preribosomal complexes, as a similar set of co-purifying proteins is recovered with the Spb1_C domain alone. FTSJ3 complexes share ~50% of components with complexes described for RPS19, Par14, nucleolin, and NOP56.","method":"FLAG-tag coimmunoprecipitation followed by mass spectrometry (proteomics); domain-deletion co-IP with Spb1_C domain","journal":"Journal of proteome research","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — MS-based interactome with domain-level functional mapping, single lab","pmids":["22540864"],"is_preprint":false},{"year":2023,"finding":"FTSJ3-mediated 2'-O-methylation of HIV-1 genomic RNA protects the virus from degradation by the antiviral exonuclease ISG20. Biochemical experiments showed that ISG20-mediated RNA degradation pauses two nucleotides upstream of and at 2'-O-methylated residues; structure-function analysis identified a steric clash between ISG20 residues R53 and D90 and the 2'-O-methyl group. HIV-1 produced in FTSJ3-KO cells (hypomethylated) is more susceptible to ISG20-mediated degradation in vitro and shows impaired reverse transcription in T cells in the presence of IFN-induced ISG20.","method":"In vitro RNA degradation assays; structure-function mutagenesis of ISG20 (R53, D90); FTSJ3-KO cell line; reverse transcription assays in primary T cells","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — in vitro biochemical assay with mutagenesis plus cellular validation in FTSJ3-KO cells, multiple orthogonal methods","pmids":["36354007"],"is_preprint":false},{"year":2024,"finding":"2'-O-methylation installed by FTSJ3 on the HIV-1 genome negatively affects HIV-1 reverse transcriptase (RT) activity. Endogenous reverse transcription assays on methylated vs. hypomethylated HIV-1 particles show that methylation impedes RT, especially at low dNTP concentrations (mimicking quiescent cells), by reducing nucleotide incorporation efficiency and impairing translocation. Mutagenesis identified K70 of reverse transcriptase as a critical residue for RT to bypass 2'-O-methylated sites.","method":"Endogenous reverse transcription assays on FTSJ3-methylated vs. FTSJ3-KO hypomethylated particles; biochemical RT assays; site-directed mutagenesis of RT (K70)","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro biochemical reconstitution, site-directed mutagenesis, and cell-based assays; single lab but multiple orthogonal methods","pmids":["38015463"],"is_preprint":false},{"year":2024,"finding":"FTSJ3 suppresses double-stranded RNA (dsRNA)-induced IFNβ signaling in hepatocellular carcinoma (HCC) cells in a 2'-O-methyltransferase-dependent manner. Deletion of RNA sensors in HCC cells or systemic knockout of type I IFN receptor IFNAR in mice rescued tumor growth defects caused by FTSJ3 deficiency, establishing that FTSJ3 promotes HCC immune evasion by suppressing the RNA sensor-mediated type I IFN pathway.","method":"FTSJ3 CRISPR knockout in HCC cells; RNA sensor double knockout; IFNAR systemic knockout mouse model; IFNβ signaling assays; in vivo tumor growth assays","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via double KO experiments in vitro and in vivo, mechanism confirmed at pathway level with multiple genetic tools","pmids":["37963197"],"is_preprint":false},{"year":2020,"finding":"CRISPRi screening identified FTSJ3 as a host factor that promotes HIV-1 latency. shRNA knockdown of FTSJ3 in primary CD4+ T cells significantly enhances HIV expression. Mechanistically, downregulation of FTSJ3 stimulates RNA Polymerase II-mediated transcription of HIV-1.","method":"Genome-wide CRISPRi screen (REACT strategy); shRNA knockdown in primary CD4+ T cells; HIV expression assays; Pol II transcription analysis","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPRi screen plus shRNA validation in primary cells, single lab but multiple cell-line contexts","pmids":["33270809"],"is_preprint":false},{"year":2025,"finding":"FTSJ3 is recruited to R-loop structures and prevents excessive R-loop formation. Depletion of FTSJ3 in lung cancer cells increases R-loop-dependent DNA damage and sensitizes cells to cisplatin both in vitro and in vivo, identifying FTSJ3 as a regulator of R-loop homeostasis and genomic stability.","method":"FTSJ3 knockdown/depletion in lung cancer cell lines; R-loop detection assays; DNA damage markers; in vitro and in vivo (xenograft) cisplatin sensitivity assays","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — KD with specific R-loop and DNA damage phenotypes, in vitro and in vivo validation, single lab","pmids":["40517939"],"is_preprint":false},{"year":2025,"finding":"FTSJ3 installs 2'-O-methylation on telomeric repeat-containing RNA (TERRA). This modification is required for recruitment of the histone methyltransferase SUV39H1 to telomeric ends, leading to H3K9 trimethylation and HP1α assembly at sub-telomeric regions. Loss of FTSJ3 destabilizes TERRA, disrupts the SUV39H1/H3K9me3/HP1 cascade, impairs heterochromatin maintenance, and causes genome instability and apoptosis selectively in hTERT-positive cancer cells.","method":"Genome-wide CRISPR/Cas9 and shRNA screens; arrayed in vitro CRISPR screen; pooled in vivo CRISPR screen; FTSJ3 depletion in isogenic hTERT+/− cell lines and patient-derived organoids; TERRA stability assays; ChIP for SUV39H1, H3K9me3, HP1α","journal":"Signal transduction and targeted therapy","confidence":"High","confidence_rationale":"Tier 2 / Strong — genome-wide screen hits validated by multiple orthogonal methods (in vitro and in vivo CRISPR, ChIP, RNA stability) across diverse models including patient-derived organoids","pmids":["42236690"],"is_preprint":false},{"year":2025,"finding":"SNORD46 guides FTSJ3 to install 2'-O-methylation on FOXO4 mRNA in glioma cells, leading to downregulation of FOXO4 expression. Loss of FOXO4 de-represses the lipogenic genes ACLY and FASN, promoting lipid metabolism and cell proliferation in glioma. The upstream regulator SRSF10 stabilizes SNORD46 by direct binding.","method":"SRSF10/SNORD46/FTSJ3 knockdown in glioma cell lines; 2'-O-methylation detection on FOXO4 mRNA; proliferation and lipid metabolism assays; promoter-binding assay for FOXO4 on ACLY/FASN","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — KD with phenotype and pathway placement, single lab, mechanism inferred from knockdown cascade without in vitro reconstitution","pmids":["40681010"],"is_preprint":false}],"current_model":"FTSJ3 is a nucleolar/nuclear RNA 2'-O-methyltransferase with multiple established functions: it participates in pre-rRNA processing and 40S ribosomal subunit biogenesis via interaction with NIP7; it is recruited by the TRBP complex to install 2'-O-methylations on the HIV-1 genome, shielding it from MDA5-mediated innate immune sensing and ISG20-mediated degradation while paradoxically also impairing viral reverse transcription; it suppresses dsRNA-triggered type I IFN signaling in cancer cells to promote immune evasion; it methylates telomeric TERRA RNA to stabilize heterochromatin at telomeres via SUV39H1/H3K9me3/HP1α in hTERT-positive cells; it regulates R-loop homeostasis to protect genomic integrity; and it can be guided by small nucleolar RNAs (e.g., SNORD46) to methylate specific mRNA targets such as FOXO4."},"narrative":{"mechanistic_narrative":"FTSJ3 is a nucleolar RNA 2'-O-methyltransferase that functions both in ribosome biogenesis and as a sequence-targeted RNA modifier across viral, telomeric, and messenger RNA substrates [PMID:22195017, PMID:30626973, PMID:42236690]. In its canonical role, FTSJ3 associates with the ribosome biogenesis factor NIP7, localizes to the nucleolus, and is required for pre-rRNA processing at sites A0, 1, and 2 in the pathway producing 18S rRNA, placing it in 40S ribosomal subunit biogenesis; its C-terminal Spb1_C domain mediates incorporation into preribosomal complexes containing both small- and large-subunit ribosomal proteins and synthesis factors [PMID:22195017, PMID:22540864]. FTSJ3 is also recruited in a DICER-independent complex with TRBP to HIV-1 genomic RNA, where it installs 2'-O-methylations that shield the viral genome from MDA5-mediated type I interferon sensing and from ISG20 exonuclease degradation—ISG20 stalling sterically at the 2'-O-methyl group—while paradoxically impeding reverse transcriptase translocation, and FTSJ3 thereby also promotes HIV-1 latency by restraining Pol II-mediated viral transcription [PMID:30626973, PMID:36354007, PMID:38015463, PMID:33270809]. The same 2'-O-methyltransferase activity suppresses dsRNA-triggered type I IFN signaling to enable hepatocellular carcinoma immune evasion [PMID:37963197]. Beyond viral RNA, FTSJ3 methylates telomeric TERRA RNA to stabilize it and drive a SUV39H1/H3K9me3/HP1α heterochromatin cascade at telomeres in hTERT-positive cancer cells, and it regulates R-loop homeostasis to protect genomic integrity [PMID:42236690, PMID:40517939]. Guided by the snoRNA SNORD46, FTSJ3 methylates FOXO4 mRNA to downregulate it and de-repress lipogenic genes in glioma [PMID:40681010].","teleology":[{"year":2011,"claim":"Established FTSJ3's first cellular function by linking it physically and functionally to ribosome biogenesis, answering where this putative methyltransferase acts.","evidence":"Yeast two-hybrid, reciprocal Co-IP and colocalization with NIP7, plus conditional knockdown with Northern analysis of pre-rRNA intermediates","pmids":["22195017"],"confidence":"High","gaps":["Did not demonstrate direct 2'-O-methylation of rRNA by FTSJ3","Catalytic requirement for the processing phenotype not tested"]},{"year":2012,"claim":"Mapped the structural determinant of FTSJ3's ribosomal engagement, showing the C-terminal Spb1_C domain mediates preribosomal complex assembly.","evidence":"FLAG Co-IP/mass spectrometry interactome with domain-deletion mapping of the Spb1_C domain","pmids":["22540864"],"confidence":"Medium","gaps":["Interactome from a single lab without orthogonal validation","Functional consequence of Spb1_C-mediated binding not assayed"]},{"year":2019,"claim":"Revealed an unexpected antiviral-evasion role: FTSJ3 in a TRBP complex methylates HIV-1 RNA to hide it from innate immune sensing, expanding its substrate range beyond rRNA.","evidence":"TRBP complex purification with MS, in vitro/ex vivo 2'O-MTase assays, RiboMethSeq site mapping, knockdown with IFN induction readout in dendritic cells","pmids":["30626973"],"confidence":"High","gaps":["Precise recognition determinants of viral target sites unresolved","Whether host mRNAs are similarly methylated not addressed here"]},{"year":2020,"claim":"Connected FTSJ3 to control of viral gene expression by identifying it as a host factor promoting HIV-1 latency through restraint of Pol II transcription.","evidence":"Genome-wide CRISPRi screen and shRNA validation in primary CD4+ T cells with HIV expression and Pol II transcription analysis","pmids":["33270809"],"confidence":"Medium","gaps":["Mechanistic link between methyltransferase activity and transcriptional repression unclear","Direct chromatin or RNA substrate at the latent provirus not defined"]},{"year":2023,"claim":"Defined a biochemical basis for viral RNA protection, showing FTSJ3-installed 2'-O-methyl groups block the antiviral exonuclease ISG20 by steric clash.","evidence":"In vitro RNA degradation assays, ISG20 R53/D90 mutagenesis, and FTSJ3-KO cells with T-cell reverse transcription assays","pmids":["36354007"],"confidence":"High","gaps":["In vivo contribution to viral fitness versus latency not quantified"]},{"year":2024,"claim":"Uncovered a paradoxical cost of methylation, demonstrating FTSJ3 marks impede HIV-1 reverse transcriptase, with K70 enabling bypass.","evidence":"Endogenous and biochemical RT assays on methylated vs hypomethylated particles with RT K70 mutagenesis","pmids":["38015463"],"confidence":"High","gaps":["How the virus balances immune shielding against impaired RT in vivo not resolved"]},{"year":2024,"claim":"Generalized the immune-evasion role to cancer, showing FTSJ3 methyltransferase activity suppresses RNA-sensor-driven type I IFN to promote tumor growth.","evidence":"FTSJ3 CRISPR KO in HCC cells, RNA sensor double KO, IFNAR systemic KO mice, and in vivo tumor assays","pmids":["37963197"],"confidence":"High","gaps":["Specific endogenous RNA substrates whose methylation prevents sensing not identified"]},{"year":2025,"claim":"Established a chromatin-level function: FTSJ3 methylates TERRA to nucleate a SUV39H1/H3K9me3/HP1α heterochromatin cascade and maintain telomere stability selectively in hTERT-positive cells.","evidence":"Genome-wide CRISPR/shRNA screens, in vivo screens, depletion in isogenic hTERT+/- lines and organoids, TERRA stability assays, and ChIP for SUV39H1/H3K9me3/HP1α","pmids":["42236690"],"confidence":"High","gaps":["Direct enzymatic methylation of TERRA in vitro and the exact methylated residues not shown","How TERRA methylation mechanistically recruits SUV39H1 unresolved"]},{"year":2025,"claim":"Linked FTSJ3 to genome protection through R-loop homeostasis, showing its loss drives R-loop-dependent DNA damage and chemosensitivity.","evidence":"Knockdown in lung cancer lines with R-loop detection, DNA damage markers, and in vitro/xenograft cisplatin sensitivity","pmids":["40517939"],"confidence":"Medium","gaps":["Whether R-loop control requires methyltransferase activity not established","Direct recruitment mechanism to R-loops undefined"]},{"year":2025,"claim":"Demonstrated snoRNA-guided mRNA targeting, with SNORD46 directing FTSJ3 to methylate FOXO4 mRNA and reprogram lipid metabolism in glioma.","evidence":"SRSF10/SNORD46/FTSJ3 knockdown in glioma cells with FOXO4 methylation detection, proliferation/lipid assays, and FOXO4 promoter-binding on ACLY/FASN","pmids":["40681010"],"confidence":"Medium","gaps":["Mechanism inferred from knockdown cascade without in vitro reconstitution of guided methylation","Direct FTSJ3-SNORD46 binding not biochemically demonstrated"]},{"year":null,"claim":"How a single nucleolar 2'-O-methyltransferase is targeted to such diverse substrates (rRNA, viral RNA, TERRA, specific mRNAs) and what governs guide/cofactor selection across these contexts remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unifying model for substrate selection across TRBP, snoRNA, and telomere contexts","Structural basis of FTSJ3 catalysis on non-rRNA substrates not determined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140098","term_label":"catalytic activity, acting on RNA","supporting_discovery_ids":[0,3,8,9]},{"term_id":"GO:0016740","term_label":"transferase activity","supporting_discovery_ids":[0,3]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,7,8]}],"localization":[{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[1]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[1,0]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[0,5]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[5,8,9]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[1,2]}],"complexes":["TRBP-FTSJ3 complex","preribosomal complex"],"partners":["TRBP","NIP7","SNORD46"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8IY81","full_name":"pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3","aliases":["Protein ftsJ homolog 3","Putative rRNA methyltransferase 3"],"length_aa":847,"mass_kda":96.6,"function":"RNA 2'-O-methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation (Microbial infection) In case of infection by HIV-1 virus, recruited to HIV-1 RNA and catalyzes 2'-O-methylation of the viral genome, allowing HIV-1 virus to escape the innate immune system (PubMed:30626973). RNA 2'-O-methylation provides a molecular signature for discrimination of self from non-self and is used by HIV-1 to evade innate immune recognition by IFIH1/MDA5 (PubMed:30626973). Mediates methylation of internal residues of HIV-1 RNA, with a strong preference for adenosine (PubMed:30626973). Recruited to HIV-1 RNA via interaction with TARBP2/TRBP (PubMed:30626973)","subcellular_location":"Nucleus, nucleolus","url":"https://www.uniprot.org/uniprotkb/Q8IY81/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/FTSJ3","classification":"Common Essential","n_dependent_lines":1106,"n_total_lines":1208,"dependency_fraction":0.9155629139072847},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"BYSL","stoichiometry":0.2},{"gene":"CSNK2B","stoichiometry":0.2},{"gene":"DRG1","stoichiometry":0.2},{"gene":"ILF3","stoichiometry":0.2},{"gene":"NPM1","stoichiometry":0.2},{"gene":"PSPC1","stoichiometry":0.2},{"gene":"RACK1","stoichiometry":0.2},{"gene":"RBM8A","stoichiometry":0.2},{"gene":"RPS16","stoichiometry":0.2},{"gene":"SRP68","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/FTSJ3","total_profiled":1310},"omim":[{"mim_id":"619204","title":"NUCLEOLAR PRE-rRNA-PROCESSING PROTEIN NIP7; NIP7","url":"https://www.omim.org/entry/619204"},{"mim_id":"618411","title":"FTSJ RNA 2-PRIME-O-METHYLTRANSFERASE 3; FTSJ3","url":"https://www.omim.org/entry/618411"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Nucleoli","reliability":"Enhanced"},{"location":"Nucleoli rim","reliability":"Enhanced"},{"location":"Mitotic chromosome","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/FTSJ3"},"hgnc":{"alias_symbol":["SPB1"],"prev_symbol":[]},"alphafold":{"accession":"Q8IY81","domains":[{"cath_id":"3.40.50.150","chopping":"15-218","consensus_level":"high","plddt":90.8948,"start":15,"end":218},{"cath_id":"-","chopping":"228-233_246-328","consensus_level":"medium","plddt":84.7521,"start":228,"end":328},{"cath_id":"-","chopping":"666-685_704-735","consensus_level":"medium","plddt":87.2733,"start":666,"end":735},{"cath_id":"-","chopping":"741-805_818-833","consensus_level":"medium","plddt":83.7691,"start":741,"end":833}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IY81","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IY81-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IY81-F1-predicted_aligned_error_v6.png","plddt_mean":70.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=FTSJ3","jax_strain_url":"https://www.jax.org/strain/search?query=FTSJ3"},"sequence":{"accession":"Q8IY81","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8IY81.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8IY81/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IY81"}},"corpus_meta":[{"pmid":"30626973","id":"PMC_30626973","title":"FTSJ3 is an RNA 2'-O-methyltransferase recruited by HIV to avoid innate immune sensing.","date":"2019","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/30626973","citation_count":173,"is_preprint":false},{"pmid":"22195017","id":"PMC_22195017","title":"The human nucleolar protein FTSJ3 associates with NIP7 and functions in pre-rRNA processing.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22195017","citation_count":32,"is_preprint":false},{"pmid":"31957540","id":"PMC_31957540","title":"Pan-cancer analysis of RNA methyltransferases identifies FTSJ3 as a potential regulator of breast cancer progression.","date":"2020","source":"RNA biology","url":"https://pubmed.ncbi.nlm.nih.gov/31957540","citation_count":31,"is_preprint":false},{"pmid":"33270809","id":"PMC_33270809","title":"Identification of unrecognized host factors promoting HIV-1 latency.","date":"2020","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/33270809","citation_count":29,"is_preprint":false},{"pmid":"36354007","id":"PMC_36354007","title":"Internal RNA 2'O-methylation in the HIV-1 genome counteracts ISG20 nuclease-mediated antiviral effect.","date":"2023","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/36354007","citation_count":24,"is_preprint":false},{"pmid":"37963197","id":"PMC_37963197","title":"RNA Methyltransferase FTSJ3 Regulates the Type I Interferon Pathway to Promote Hepatocellular Carcinoma Immune Evasion.","date":"2024","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/37963197","citation_count":17,"is_preprint":false},{"pmid":"22540864","id":"PMC_22540864","title":"Proteomic characterization of the human FTSJ3 preribosomal complexes.","date":"2012","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/22540864","citation_count":17,"is_preprint":false},{"pmid":"24595062","id":"PMC_24595062","title":"FTSJ2, a heat shock-inducible mitochondrial protein, suppresses cell invasion and migration.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24595062","citation_count":14,"is_preprint":false},{"pmid":"38330300","id":"PMC_38330300","title":"Unravelling novel and pleiotropic genes for cannon bone circumference and bone mineral density in Yorkshire pigs.","date":"2024","source":"Journal of animal science","url":"https://pubmed.ncbi.nlm.nih.gov/38330300","citation_count":9,"is_preprint":false},{"pmid":"33393450","id":"PMC_33393450","title":"A host-based whole genome sequencing study reveals novel risk loci associated with severity of influenza A(H1N1)pdm09 infection.","date":"2021","source":"Emerging microbes & 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cancer","url":"https://pubmed.ncbi.nlm.nih.gov/33752626","citation_count":4,"is_preprint":false},{"pmid":"40497153","id":"PMC_40497153","title":"HIV-1 latency: From acquaintance to confidant.","date":"2025","source":"Journal of virus eradication","url":"https://pubmed.ncbi.nlm.nih.gov/40497153","citation_count":2,"is_preprint":false},{"pmid":"40517939","id":"PMC_40517939","title":"Loss of FTSJ3 promotes R-loop-associated DNA damage and facilitates chemosensitivity in lung cancer cells.","date":"2025","source":"Cancer letters","url":"https://pubmed.ncbi.nlm.nih.gov/40517939","citation_count":1,"is_preprint":false},{"pmid":"38819277","id":"PMC_38819277","title":"[How do 2'-O-methylations within Human Immunodeficiency Virus type 1 (HIV-1) genome regulate its replication?].","date":"2024","source":"Medecine sciences : M/S","url":"https://pubmed.ncbi.nlm.nih.gov/38819277","citation_count":1,"is_preprint":false},{"pmid":"40681010","id":"PMC_40681010","title":"SNORD46 stabilized by SRSF10 regulating lipid metabolism and cell proliferation of glioma cells via mediating FOXO4 2'-O-methylation.","date":"2025","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/40681010","citation_count":0,"is_preprint":false},{"pmid":"42236690","id":"PMC_42236690","title":"Epigenetic control of telomeric RNA maintains heterochromatin in telomerase-driven cancers.","date":"2026","source":"Signal transduction and targeted therapy","url":"https://pubmed.ncbi.nlm.nih.gov/42236690","citation_count":0,"is_preprint":false},{"pmid":"41816574","id":"PMC_41816574","title":"FTSJ1-mediated IL1RN mRNA instability promotes inflammation-driven hepatocellular carcinoma.","date":"2026","source":"Journal of gastrointestinal oncology","url":"https://pubmed.ncbi.nlm.nih.gov/41816574","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.01.26.634101","title":"Epigenetic Control of TERRA by FTSJ3 is Critical for Telomerase-Driven Cancers","date":"2025-01-27","source":"bioRxiv","url":"https://doi.org/10.1101/2025.01.26.634101","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":12096,"output_tokens":3249,"usd":0.042512,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10711,"output_tokens":3687,"usd":0.072865,"stage2_stop_reason":"end_turn"},"total_usd":0.115377,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"FTSJ3 is a 2'-O-methyltransferase (2'O-MTase) that forms a DICER-independent complex with TRBP (TAR RNA-binding protein). This complex is recruited to HIV-1 RNA via TRBP, where FTSJ3 installs 2'-O-methylations at specific residues on the viral genome. Hypomethylated HIV-1 produced in FTSJ3 knockdown cells triggers MDA5-mediated type I interferon (IFN-α and IFN-β) responses in human dendritic cells, demonstrating that FTSJ3-mediated 2'-O-methylation shields HIV-1 RNA from innate immune sensing.\",\n      \"method\": \"TRBP complex purification and mass spectrometry; in vitro and ex vivo 2'O-MTase activity assays; RiboMethSeq mapping of methylation sites; shRNA knockdown; IFN induction assays in human dendritic cells\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (biochemical purification, in vitro enzymatic assay, RiboMethSeq, KD with functional IFN readout) in a single rigorous study\",\n      \"pmids\": [\"30626973\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"FTSJ3 physically associates with human NIP7 (a ribosome biogenesis factor) and localizes to the nucleolus. Conditional knockdown of FTSJ3 causes accumulation of the 34S pre-rRNA (spanning site A' to site 2b), indicating that FTSJ3 is required for efficient processing at sites A0, 1, and 2 in the pathway leading to 18S rRNA maturation, implicating FTSJ3 in 40S ribosomal subunit biogenesis.\",\n      \"method\": \"Yeast two-hybrid; coimmunoprecipitation; colocalization (immunofluorescence); conditional shRNA knockdown; Northern blot analysis of pre-rRNA processing intermediates\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, colocalization, KD with specific pre-rRNA processing phenotype, multiple orthogonal methods in one study\",\n      \"pmids\": [\"22195017\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"FLAG-tagged FTSJ3 coimmunoprecipitates both small (RPS) and large (RPL) ribosomal proteins as well as ribosome synthesis factors in preribosomal complexes. The C-terminal Spb1_C domain of FTSJ3 mediates its interaction with preribosomal complexes, as a similar set of co-purifying proteins is recovered with the Spb1_C domain alone. FTSJ3 complexes share ~50% of components with complexes described for RPS19, Par14, nucleolin, and NOP56.\",\n      \"method\": \"FLAG-tag coimmunoprecipitation followed by mass spectrometry (proteomics); domain-deletion co-IP with Spb1_C domain\",\n      \"journal\": \"Journal of proteome research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — MS-based interactome with domain-level functional mapping, single lab\",\n      \"pmids\": [\"22540864\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"FTSJ3-mediated 2'-O-methylation of HIV-1 genomic RNA protects the virus from degradation by the antiviral exonuclease ISG20. Biochemical experiments showed that ISG20-mediated RNA degradation pauses two nucleotides upstream of and at 2'-O-methylated residues; structure-function analysis identified a steric clash between ISG20 residues R53 and D90 and the 2'-O-methyl group. HIV-1 produced in FTSJ3-KO cells (hypomethylated) is more susceptible to ISG20-mediated degradation in vitro and shows impaired reverse transcription in T cells in the presence of IFN-induced ISG20.\",\n      \"method\": \"In vitro RNA degradation assays; structure-function mutagenesis of ISG20 (R53, D90); FTSJ3-KO cell line; reverse transcription assays in primary T cells\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — in vitro biochemical assay with mutagenesis plus cellular validation in FTSJ3-KO cells, multiple orthogonal methods\",\n      \"pmids\": [\"36354007\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"2'-O-methylation installed by FTSJ3 on the HIV-1 genome negatively affects HIV-1 reverse transcriptase (RT) activity. Endogenous reverse transcription assays on methylated vs. hypomethylated HIV-1 particles show that methylation impedes RT, especially at low dNTP concentrations (mimicking quiescent cells), by reducing nucleotide incorporation efficiency and impairing translocation. Mutagenesis identified K70 of reverse transcriptase as a critical residue for RT to bypass 2'-O-methylated sites.\",\n      \"method\": \"Endogenous reverse transcription assays on FTSJ3-methylated vs. FTSJ3-KO hypomethylated particles; biochemical RT assays; site-directed mutagenesis of RT (K70)\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro biochemical reconstitution, site-directed mutagenesis, and cell-based assays; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"38015463\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"FTSJ3 suppresses double-stranded RNA (dsRNA)-induced IFNβ signaling in hepatocellular carcinoma (HCC) cells in a 2'-O-methyltransferase-dependent manner. Deletion of RNA sensors in HCC cells or systemic knockout of type I IFN receptor IFNAR in mice rescued tumor growth defects caused by FTSJ3 deficiency, establishing that FTSJ3 promotes HCC immune evasion by suppressing the RNA sensor-mediated type I IFN pathway.\",\n      \"method\": \"FTSJ3 CRISPR knockout in HCC cells; RNA sensor double knockout; IFNAR systemic knockout mouse model; IFNβ signaling assays; in vivo tumor growth assays\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via double KO experiments in vitro and in vivo, mechanism confirmed at pathway level with multiple genetic tools\",\n      \"pmids\": [\"37963197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CRISPRi screening identified FTSJ3 as a host factor that promotes HIV-1 latency. shRNA knockdown of FTSJ3 in primary CD4+ T cells significantly enhances HIV expression. Mechanistically, downregulation of FTSJ3 stimulates RNA Polymerase II-mediated transcription of HIV-1.\",\n      \"method\": \"Genome-wide CRISPRi screen (REACT strategy); shRNA knockdown in primary CD4+ T cells; HIV expression assays; Pol II transcription analysis\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPRi screen plus shRNA validation in primary cells, single lab but multiple cell-line contexts\",\n      \"pmids\": [\"33270809\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FTSJ3 is recruited to R-loop structures and prevents excessive R-loop formation. Depletion of FTSJ3 in lung cancer cells increases R-loop-dependent DNA damage and sensitizes cells to cisplatin both in vitro and in vivo, identifying FTSJ3 as a regulator of R-loop homeostasis and genomic stability.\",\n      \"method\": \"FTSJ3 knockdown/depletion in lung cancer cell lines; R-loop detection assays; DNA damage markers; in vitro and in vivo (xenograft) cisplatin sensitivity assays\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — KD with specific R-loop and DNA damage phenotypes, in vitro and in vivo validation, single lab\",\n      \"pmids\": [\"40517939\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"FTSJ3 installs 2'-O-methylation on telomeric repeat-containing RNA (TERRA). This modification is required for recruitment of the histone methyltransferase SUV39H1 to telomeric ends, leading to H3K9 trimethylation and HP1α assembly at sub-telomeric regions. Loss of FTSJ3 destabilizes TERRA, disrupts the SUV39H1/H3K9me3/HP1 cascade, impairs heterochromatin maintenance, and causes genome instability and apoptosis selectively in hTERT-positive cancer cells.\",\n      \"method\": \"Genome-wide CRISPR/Cas9 and shRNA screens; arrayed in vitro CRISPR screen; pooled in vivo CRISPR screen; FTSJ3 depletion in isogenic hTERT+/− cell lines and patient-derived organoids; TERRA stability assays; ChIP for SUV39H1, H3K9me3, HP1α\",\n      \"journal\": \"Signal transduction and targeted therapy\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genome-wide screen hits validated by multiple orthogonal methods (in vitro and in vivo CRISPR, ChIP, RNA stability) across diverse models including patient-derived organoids\",\n      \"pmids\": [\"42236690\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"SNORD46 guides FTSJ3 to install 2'-O-methylation on FOXO4 mRNA in glioma cells, leading to downregulation of FOXO4 expression. Loss of FOXO4 de-represses the lipogenic genes ACLY and FASN, promoting lipid metabolism and cell proliferation in glioma. The upstream regulator SRSF10 stabilizes SNORD46 by direct binding.\",\n      \"method\": \"SRSF10/SNORD46/FTSJ3 knockdown in glioma cell lines; 2'-O-methylation detection on FOXO4 mRNA; proliferation and lipid metabolism assays; promoter-binding assay for FOXO4 on ACLY/FASN\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — KD with phenotype and pathway placement, single lab, mechanism inferred from knockdown cascade without in vitro reconstitution\",\n      \"pmids\": [\"40681010\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"FTSJ3 is a nucleolar/nuclear RNA 2'-O-methyltransferase with multiple established functions: it participates in pre-rRNA processing and 40S ribosomal subunit biogenesis via interaction with NIP7; it is recruited by the TRBP complex to install 2'-O-methylations on the HIV-1 genome, shielding it from MDA5-mediated innate immune sensing and ISG20-mediated degradation while paradoxically also impairing viral reverse transcription; it suppresses dsRNA-triggered type I IFN signaling in cancer cells to promote immune evasion; it methylates telomeric TERRA RNA to stabilize heterochromatin at telomeres via SUV39H1/H3K9me3/HP1α in hTERT-positive cells; it regulates R-loop homeostasis to protect genomic integrity; and it can be guided by small nucleolar RNAs (e.g., SNORD46) to methylate specific mRNA targets such as FOXO4.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"FTSJ3 is a nucleolar RNA 2'-O-methyltransferase that functions both in ribosome biogenesis and as a sequence-targeted RNA modifier across viral, telomeric, and messenger RNA substrates [#1, #0, #8]. In its canonical role, FTSJ3 associates with the ribosome biogenesis factor NIP7, localizes to the nucleolus, and is required for pre-rRNA processing at sites A0, 1, and 2 in the pathway producing 18S rRNA, placing it in 40S ribosomal subunit biogenesis; its C-terminal Spb1_C domain mediates incorporation into preribosomal complexes containing both small- and large-subunit ribosomal proteins and synthesis factors [#1, #2]. FTSJ3 is also recruited in a DICER-independent complex with TRBP to HIV-1 genomic RNA, where it installs 2'-O-methylations that shield the viral genome from MDA5-mediated type I interferon sensing and from ISG20 exonuclease degradation—ISG20 stalling sterically at the 2'-O-methyl group—while paradoxically impeding reverse transcriptase translocation, and FTSJ3 thereby also promotes HIV-1 latency by restraining Pol II-mediated viral transcription [#0, #3, #4, #6]. The same 2'-O-methyltransferase activity suppresses dsRNA-triggered type I IFN signaling to enable hepatocellular carcinoma immune evasion [#5]. Beyond viral RNA, FTSJ3 methylates telomeric TERRA RNA to stabilize it and drive a SUV39H1/H3K9me3/HP1α heterochromatin cascade at telomeres in hTERT-positive cancer cells, and it regulates R-loop homeostasis to protect genomic integrity [#8, #7]. Guided by the snoRNA SNORD46, FTSJ3 methylates FOXO4 mRNA to downregulate it and de-repress lipogenic genes in glioma [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"Established FTSJ3's first cellular function by linking it physically and functionally to ribosome biogenesis, answering where this putative methyltransferase acts.\",\n      \"evidence\": \"Yeast two-hybrid, reciprocal Co-IP and colocalization with NIP7, plus conditional knockdown with Northern analysis of pre-rRNA intermediates\",\n      \"pmids\": [\"22195017\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not demonstrate direct 2'-O-methylation of rRNA by FTSJ3\", \"Catalytic requirement for the processing phenotype not tested\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Mapped the structural determinant of FTSJ3's ribosomal engagement, showing the C-terminal Spb1_C domain mediates preribosomal complex assembly.\",\n      \"evidence\": \"FLAG Co-IP/mass spectrometry interactome with domain-deletion mapping of the Spb1_C domain\",\n      \"pmids\": [\"22540864\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interactome from a single lab without orthogonal validation\", \"Functional consequence of Spb1_C-mediated binding not assayed\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Revealed an unexpected antiviral-evasion role: FTSJ3 in a TRBP complex methylates HIV-1 RNA to hide it from innate immune sensing, expanding its substrate range beyond rRNA.\",\n      \"evidence\": \"TRBP complex purification with MS, in vitro/ex vivo 2'O-MTase assays, RiboMethSeq site mapping, knockdown with IFN induction readout in dendritic cells\",\n      \"pmids\": [\"30626973\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Precise recognition determinants of viral target sites unresolved\", \"Whether host mRNAs are similarly methylated not addressed here\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connected FTSJ3 to control of viral gene expression by identifying it as a host factor promoting HIV-1 latency through restraint of Pol II transcription.\",\n      \"evidence\": \"Genome-wide CRISPRi screen and shRNA validation in primary CD4+ T cells with HIV expression and Pol II transcription analysis\",\n      \"pmids\": [\"33270809\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between methyltransferase activity and transcriptional repression unclear\", \"Direct chromatin or RNA substrate at the latent provirus not defined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Defined a biochemical basis for viral RNA protection, showing FTSJ3-installed 2'-O-methyl groups block the antiviral exonuclease ISG20 by steric clash.\",\n      \"evidence\": \"In vitro RNA degradation assays, ISG20 R53/D90 mutagenesis, and FTSJ3-KO cells with T-cell reverse transcription assays\",\n      \"pmids\": [\"36354007\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo contribution to viral fitness versus latency not quantified\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Uncovered a paradoxical cost of methylation, demonstrating FTSJ3 marks impede HIV-1 reverse transcriptase, with K70 enabling bypass.\",\n      \"evidence\": \"Endogenous and biochemical RT assays on methylated vs hypomethylated particles with RT K70 mutagenesis\",\n      \"pmids\": [\"38015463\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How the virus balances immune shielding against impaired RT in vivo not resolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Generalized the immune-evasion role to cancer, showing FTSJ3 methyltransferase activity suppresses RNA-sensor-driven type I IFN to promote tumor growth.\",\n      \"evidence\": \"FTSJ3 CRISPR KO in HCC cells, RNA sensor double KO, IFNAR systemic KO mice, and in vivo tumor assays\",\n      \"pmids\": [\"37963197\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Specific endogenous RNA substrates whose methylation prevents sensing not identified\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Established a chromatin-level function: FTSJ3 methylates TERRA to nucleate a SUV39H1/H3K9me3/HP1α heterochromatin cascade and maintain telomere stability selectively in hTERT-positive cells.\",\n      \"evidence\": \"Genome-wide CRISPR/shRNA screens, in vivo screens, depletion in isogenic hTERT+/- lines and organoids, TERRA stability assays, and ChIP for SUV39H1/H3K9me3/HP1α\",\n      \"pmids\": [\"42236690\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct enzymatic methylation of TERRA in vitro and the exact methylated residues not shown\", \"How TERRA methylation mechanistically recruits SUV39H1 unresolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Linked FTSJ3 to genome protection through R-loop homeostasis, showing its loss drives R-loop-dependent DNA damage and chemosensitivity.\",\n      \"evidence\": \"Knockdown in lung cancer lines with R-loop detection, DNA damage markers, and in vitro/xenograft cisplatin sensitivity\",\n      \"pmids\": [\"40517939\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether R-loop control requires methyltransferase activity not established\", \"Direct recruitment mechanism to R-loops undefined\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Demonstrated snoRNA-guided mRNA targeting, with SNORD46 directing FTSJ3 to methylate FOXO4 mRNA and reprogram lipid metabolism in glioma.\",\n      \"evidence\": \"SRSF10/SNORD46/FTSJ3 knockdown in glioma cells with FOXO4 methylation detection, proliferation/lipid assays, and FOXO4 promoter-binding on ACLY/FASN\",\n      \"pmids\": [\"40681010\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism inferred from knockdown cascade without in vitro reconstitution of guided methylation\", \"Direct FTSJ3-SNORD46 binding not biochemically demonstrated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How a single nucleolar 2'-O-methyltransferase is targeted to such diverse substrates (rRNA, viral RNA, TERRA, specific mRNAs) and what governs guide/cofactor selection across these contexts remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unifying model for substrate selection across TRBP, snoRNA, and telomere contexts\", \"Structural basis of FTSJ3 catalysis on non-rRNA substrates not determined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140098\", \"supporting_discovery_ids\": [0, 3, 8, 9]},\n      {\"term_id\": \"GO:0016740\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 7, 8]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [1, 0]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [5, 8, 9]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [\"TRBP-FTSJ3 complex\", \"preribosomal complex\"],\n    \"partners\": [\"TRBP\", \"NIP7\", \"SNORD46\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}