{"gene":"RPL10","run_date":"2026-06-10T06:43:37","timeline":{"discoveries":[{"year":1982,"finding":"The ribosomal protein L10-L12 complex binds specifically to the leader sequence of the L10 operon mRNA, preventing translation of L10 and L12 proteins. rRNA prevents this binding, and extended sequence homologies between 23S rRNA and the L10 leader RNA were identified, suggesting the L10-L12 complex can be sequestered into assembling 50S subunits to relieve translational repression.","method":"mRNA binding assay, deletion/point mutation analysis of leader RNA, rRNA competition assay","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal in vitro binding and mutational analyses; replicated by independent work (PMID:6994102, PMID:379826)","pmids":["6765237"],"is_preprint":false},{"year":1980,"finding":"E. coli ribosomal protein L10 autoregulates its own translation in vitro: addition of exogenous L10 inhibits L10 synthesis but not L12, beta/beta'-RNA polymerase subunit, or EF-Tu synthesis. Inhibition occurs at the level of translation, not mRNA degradation.","method":"DNA-dependent cell-free protein synthesis (in vitro translation assay) with purified L10","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct in vitro reconstitution assay showing autogenous translational repression, consistent with PMID:6765237","pmids":["6994102"],"is_preprint":false},{"year":1979,"finding":"Chemical modification of arginine residues in E. coli ribosomal protein L10 inhibits its binding to ribosomes and 23S rRNA but does not affect its ability to bind four molecules of L7/L12. This suggests L10 uses separate domains for rRNA/ribosome binding versus L7/L12 interaction, and its role in promoting L7/L12 ribosome association is mediated through simultaneous binding to both 23S rRNA and L7/L12.","method":"Chemical modification (arginine-specific reagents) of L10 followed by binding assays with ribosomes, 23S rRNA, and L7/L12","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — chemical modification plus multiple binding assays in single study; single lab","pmids":["379826"],"is_preprint":false},{"year":1989,"finding":"Structural and sequence analysis revealed that eukaryotic and archaebacterial L10 proteins contain approximately three-fourths of an L12 protein sequence fused to their C-terminus, with a repeated 26-amino acid module present in two copies in eukaryotes that may mediate L12 dimerization and L10-L12 complex formation.","method":"Comparative sequence analysis of cloned L10 genes from Halobacterium, Sulfolobus, and Saccharomyces cerevisiae","journal":"Canadian journal of microbiology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/sequence analysis only, no direct functional experiment","pmids":["2497941"],"is_preprint":false},{"year":1990,"finding":"E. coli ribosomal protein L10 is rapidly proteolytically degraded when synthesized in excess of L7/L12. L7/L12 stabilizes L10 by forming a complex with it; free L10 (not complexed with L7/L12) is subject to rapid proteolytic decay, contributing to balanced stoichiometric expression of both proteins.","method":"Genetic manipulation of rplL ribosome-binding site, overproduction in trans, pulse-chase analysis of protein stability","journal":"Journal of bacteriology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo genetic and biochemical experiments demonstrating proteolytic regulation; single lab","pmids":["2403546"],"is_preprint":false},{"year":1996,"finding":"Rat ribosomal protein L10 was found to be the mammalian homolog of the chicken Jun-binding protein (Jif-1) and nearly identical to a putative Wilms' tumor suppressor (QM), indicating conservation of potential extraribosomal functions. The protein has 213 amino acids (N-terminal Met removed post-translationally) with a molecular weight of 24,456 Da.","method":"cDNA sequencing, N-terminal amino acid sequencing, Southern blot hybridization","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct protein sequencing and molecular characterization; single lab","pmids":["8780716"],"is_preprint":false},{"year":1998,"finding":"The human QM protein (RPL10) assembles onto the 60S ribosomal subunit in the cytoplasm, not in the nucleolus. Immunofluorescence co-localization showed QM co-localizes with the large P-antigen (60S core ribosomal protein) only in the cytoplasm at the rough endoplasmic reticulum, consistent with a role in a late step of 60S subunit assembly.","method":"Indirect immunofluorescence co-localization with core 60S ribosomal protein (large P-antigen) in human cells","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional interpretation; single lab, one orthogonal method","pmids":["9443083"],"is_preprint":false},{"year":2002,"finding":"The QM protein (RPL10) interacts with the SH3 domain of the proto-oncogene c-Yes kinase through two distinct regions of QM (neither containing canonical SH3 binding motifs), reduces c-Yes kinase activity by ~70%, and inhibits c-Yes autophosphorylation. QM overexpression also increases c-Yes protein and mRNA levels. Co-localization in tumor cell lines was demonstrated by immunofluorescence.","method":"SH3 domain pull-down/co-IP, in vitro kinase activity assay, autophosphorylation assay, immunofluorescence co-localization","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple in vitro assays plus cell-based co-localization; single lab","pmids":["12138090"],"is_preprint":false},{"year":2003,"finding":"E. histolytica L10 (EhL10, homologous to human QM/RPL10) is part of the ribosomal complex, localizes primarily to the nucleus of trophozoites, and overexpression reduces cellular growth by 60%. DNA mobility-shift assays showed EhL10 can destabilize the AP-1 (activating protein 1) complex by binding specifically to the c-Jun-like protein, suggesting an extraribosomal function in suppressing c-Jun-dependent gene transcription.","method":"Western blot fractionation, immunofluorescence, overexpression growth assay, DNA mobility-shift (EMSA) assay","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — multiple assays in parasite model orthologous to human RPL10; single lab","pmids":["12672524"],"is_preprint":false},{"year":2004,"finding":"In yeast, rpL10/Grc5p functionally interacts with the nuclear export factor Nmd3p to modulate the cellular polysome complement, and with small subunit protein rpS6 in 40S/60S subunit joining and differential protein expression.","method":"Genetic and biochemical analysis of polysome profiles, subunit joining assays, functional interaction studies in S. cerevisiae","journal":"FEMS yeast research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple functional assays in yeast model; single lab","pmids":["15556089"],"is_preprint":false},{"year":2006,"finding":"Two missense mutations (L206M and H213Q) in human RPL10 identified in autism patients confer hypomorphism with respect to translational regulation while preserving basic translation function, as assessed using yeast as a model system with aberrant ribosomal profiles.","method":"Yeast complementation/ribosomal profile analysis with patient-derived RPL10 mutants","journal":"Molecular psychiatry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional yeast assay with disease mutants showing ribosomal profiling defects; single lab","pmids":["16940977"],"is_preprint":false},{"year":2006,"finding":"Heterozygosity for rpl10Δ in yeast reduces the translating ribosome population and increases replicative lifespan by 24%, linking RPL10 gene dosage to modulation of translation and aging.","method":"Yeast deletion genetics, polysome profiling, replicative lifespan assay","journal":"Experimental gerontology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct genetic experiment with multiple readouts in yeast; single lab","pmids":["17174052"],"is_preprint":false},{"year":2007,"finding":"Extensive mutational analysis of yeast Rpl10 showed that mutations in a central loop (residues 102–112) significantly impair release of the 60S nuclear export adapter Nmd3, while Rpl10 mutants unable to bind the ribosome accumulate in the nucleus, suggesting a nuclear role. The central loop is unstructured in prokaryotic crystal/solution structures and plays a dynamic role in ribosome function or factor regulation.","method":"Systematic mutagenesis of RPL10, Nmd3 release assays, subcellular localization analysis in S. cerevisiae","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — extensive mutational analysis with multiple functional readouts; domain mapping consistent with structural data","pmids":["17761675"],"is_preprint":false},{"year":2008,"finding":"Yeast ribosomal protein L10's N-terminal 'hook' (which inserts into 25S rRNA helix 89 bulge) controls tRNA movement through the large subunit. Mutations in this domain cause broad effects on rRNA structure along the tRNA 3' end path, ribosome biogenesis, elongation factor binding, drug resistance, and translational fidelity, indicating L10 transduces conformational information through the ribosome.","method":"Yeast mutagenesis, killer virus maintenance assay (proxy for 60S defects), rRNA chemical modification (SHAPE/DMS), drug sensitivity, translational fidelity assays","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal biochemical and genetic assays; rRNA structural probing plus functional analyses","pmids":["18824477"],"is_preprint":false},{"year":2008,"finding":"The L10(L12)4 pentameric complex binds both mRNA leader and rRNA targets using structurally similar kink-turn RNA motifs. The ribosomal protein L11 enhances L10(L12)4 binding to rRNA by ~100-fold through a protein-protein interaction, ensuring saturation of the ribosomal binding site. mRNA and rRNA targets use equivalent kink-turn and loop-AA recognition elements but in different structural contexts.","method":"Fluorescence binding assays, mutagenesis of kink-turn motifs in mRNA and rRNA, quantitative affinity measurements using Bacillus stearothermophilus L10(L12)4","journal":"Biochemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — quantitative binding assays, mutagenesis, fluorescence methods; multiple orthogonal approaches in single rigorous study","pmids":["18247578"],"is_preprint":false},{"year":2012,"finding":"Recurrent somatic mutations in RPL10 (most notably Arg98Ser, R98S) are found in ~10% of pediatric T-ALL patients. Yeast and lymphoid cells expressing RPL10 R98S showed a ribosome biogenesis defect.","method":"Exome sequencing of T-ALL patients, functional validation in yeast and lymphoid cells (ribosomal profiling)","journal":"Nature genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — patient mutation discovery plus functional ribosome biogenesis assay; replicated in two model systems","pmids":["23263491"],"is_preprint":false},{"year":2013,"finding":"An internal loop in yeast rpL10 acts as a central controller of ribosomal intersubunit rotation. Mutations in this loop cause opposing shifts in the rotational equilibrium between non-rotated and rotated ribosomal states, with allosteric effects propagating through both subunits and linking all functional centers. An rpL3 mutation with opposing structural effects suppresses an rpL10 mutant by re-establishing rotational equilibrium. The rpL10 loop is also involved in Sdo1p recruitment, linking rotational status to late-stage 60S maturation.","method":"rRNA chemical modification (DMS), ribosomal frameshifting assays, translational fidelity assays, genetic suppressor analysis, biochemical elongation factor binding assays in S. cerevisiae","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — multiple orthogonal methods (chemical probing, genetics, biochemistry, fidelity assays) in single comprehensive study; suppressor genetics validate mechanism","pmids":["24214990"],"is_preprint":false},{"year":2014,"finding":"A novel RPL10 missense mutation (p.K78E) causes X-linked microcephaly with seizures and growth retardation. Zebrafish rpl10 knockdown decreases head size with reduced bulk translation and increased apoptosis in the brain. In vivo complementation showed p.K78E is a loss-of-function variant. RPL10 is in close proximity to the peptidyl transferase active site of the 60S subunit.","method":"Zebrafish morpholino knockdown, bulk translation assays, apoptosis assays, in vivo complementation with wildtype vs mutant RPL10","journal":"Genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal functional assays in zebrafish model with rescue experiment; direct loss-of-function phenotype linked to translation","pmids":["25316788"],"is_preprint":false},{"year":2014,"finding":"The antituberculosis antibiotic capreomycin inhibits the L12-L10 protein-protein interaction, thereby inhibiting elongation factor G-dependent GTPase activity and ribosome-mediated protein synthesis. Overexpression of L12 and/or L10 increases capreomycin MIC, and blocking protein synthesis with thiostrepton restrains capreomycin bactericidal activity.","method":"L12-L10 interaction assay, MIC measurements, in vitro GTPase activity assay, in vitro protein synthesis assay","journal":"Antimicrobial agents and chemotherapy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple biochemical assays; bacterial L10 ortholog; single lab","pmids":["24449778"],"is_preprint":false},{"year":2015,"finding":"A novel RPL10 missense mutation (p.A64V) in the N-terminal domain causes X-linked intellectual disability with cerebellar hypoplasia and spondylo-epiphyseal dysplasia. Unlike other RPL10 mutations, the A64V variant generates a functional ribosomal protein able to complement yeast translational defects but results in an increase in the actively translating ribosome population.","method":"Yeast complementation assay, polysome profiling, translational capacity measurement","journal":"Human mutation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — yeast functional assays showing gain-of-translation phenotype; single lab","pmids":["26290468"],"is_preprint":false},{"year":2015,"finding":"In Bacillus subtilis, the ribosomal protein L10(L12)4 complex autoregulates rplJL operon expression by a transcription attenuation mechanism: L10(L12)4 binds to an anti-antiterminator RNA structure in the rplJL leader transcript, stabilizing it and promoting formation of an intrinsic terminator, thereby repressing transcription. This is distinct from the E. coli translational repression mechanism.","method":"Transcriptional and translational fusions, RNA binding studies, in vitro transcription, competitor oligonucleotides, in vivo mutational analysis","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro transcription, RNA binding, and multiple in vivo mutational validations; multiple orthogonal methods in single study","pmids":["26101249"],"is_preprint":false},{"year":2016,"finding":"Crystal structures of the eubacterial large ribosomal subunit in complex with orthosomycin antibiotics (avilamycin and evernimicin) revealed that ribosomal protein uL16 (RPL10 bacterial ortholog) participates in binding and discriminating A-tRNA at the A-tRNA entrance corridor. Structural analysis showed that differences in the α1 helix length of uL16 between eukaryotes and prokaryotes are key determinants of drug selectivity.","method":"High-resolution X-ray crystallography of large ribosomal subunit–antibiotic complexes","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution crystal structures providing mechanistic detail about uL16 role in A-tRNA discrimination and antibiotic selectivity","pmids":["27791159"],"is_preprint":false},{"year":2017,"finding":"The T-ALL-associated RPL10 R98S mutation causes failure to release the 60S export adapter Nmd3 from the ribosomal P site. In vitro reconstitution showed Nmd3 inhibits Sdo1-stimulated Efl1 GTPase activity on RPL10 R98S but not wild-type 60S subunits. Suppressor mutations in Nmd3 and Tif6 that disrupted Nmd3-ribosome or Nmd3-Tif6 interactions rescued the defect in vivo and in vitro, defining the molecular defect of RPL10 R98S.","method":"In vitro reconstitution with purified components, Nmd3 release assays, Efl1 GTPase activity assays, suppressor genetic screen, yeast genetics","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution with purified components plus in vivo genetic suppressor validation; multiple orthogonal approaches","pmids":["28715419"],"is_preprint":false},{"year":2017,"finding":"The RPL10 R98S mutation causes overexpression of JAK-STAT signaling proteins in mouse lymphoid cells. RPL10 R98S expressing cells display JAK-STAT pathway hyper-activation upon cytokine stimulation. Mechanistically, RPL10 R98S reduces apparent programmed ribosomal frameshifting at JAK-STAT gene frameshift signals and decreases JAK1 degradation. RPL10 R98S cells also show reduced proteasome activity.","method":"Proteome screen, transgenic mouse model, xenograft T-ALL samples, cytokine stimulation assays, ribosomal frameshift reporter assays, proteasome activity assays","journal":"Leukemia","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods across mouse model, human xenograft, and cell-based systems; multiple labs contribute validation","pmids":["28744013"],"is_preprint":false},{"year":2018,"finding":"RPL10 R98S mutant leukemia cells accumulate reactive oxygen species, causing mitochondrial dysfunction and reduced ATP levels, leading to a proliferation defect. These cells survive oxidative stress via specific upregulation of IRES-mediated translation of BCL-2 anti-apoptotic factor, resulting in BCL-2 protein overexpression and sensitivity to the BCL-2 inhibitor Venetoclax.","method":"ROS measurement, mitochondrial function assays, ATP quantification, IRES reporter assays, BCL-2 protein quantification, xenograft mouse model with Venetoclax treatment","journal":"Leukemia","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal mechanistic assays plus in vivo xenograft validation; novel mechanism defined by IRES reporter and ROS measurements","pmids":["29930300"],"is_preprint":false},{"year":2018,"finding":"RPL10 in mitochondria of pancreatic cancer cells regulates ROS levels by affecting mitochondrial Complex I activity. ChIP-seq showed RPL10 is unlikely to function as a transcription factor. Transcriptome analysis indicated RPL10 regulates expression of proteins related to ROS production.","method":"Chromatin immunoprecipitation sequencing (ChIP-seq), transcriptome analysis, mitochondrial Complex I activity assay, ROS measurement","journal":"Redox biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical assay of Complex I activity plus ChIP-seq; single lab, mechanistic follow-up limited","pmids":["30172100"],"is_preprint":false},{"year":2023,"finding":"RPL10 undergoes ufmylation (UFM1 modification) in pancreatic cancer tissues and cell lines, with specific modification sites identified and verified by mutagenesis. RPL10 ufmylation increases cell proliferation and stemness primarily through upregulation of the transcription factor KLF4. Mutagenesis of ufmylation sites in RPL10 confirmed the connection between ufmylation and these cellular phenotypes.","method":"Mass spectrometry identification of ufmylation sites, site-directed mutagenesis, cell proliferation assays, stemness assays, KLF4 expression analysis in patient tissues and cell lines","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — PTM site identification plus mutagenesis validation with cellular readouts; single lab","pmids":["37280198"],"is_preprint":false}],"current_model":"RPL10 (QM/uL16) is an essential component of the 60S large ribosomal subunit that acts as a central regulator of ribosome function: its internal loop controls intersubunit rotation and drives the elongation cycle, its N-terminal hook coordinates tRNA movement through the large subunit, and it is required at a late cytoplasmic step for 60S maturation by enabling release of the export adapter Nmd3 (via Sdo1-stimulated Efl1 GTPase activity) and facilitating joining with the 40S subunit; beyond its ribosomal role, RPL10 autoregulates its own synthesis by forming an L10-L12 complex that binds the mRNA leader to repress translation, is stabilized by complex formation with L12 (free L10 is rapidly degraded), can suppress c-Yes kinase activity through direct SH3 domain interaction, and undergoes ufmylation that promotes cancer cell stemness; oncogenic mutations such as R98S trap Nmd3 in the P site, impair programmed ribosomal frameshifting at JAK-STAT genes, enhance IRES-dependent BCL-2 translation, and accumulate ROS via mitochondrial Complex I, collectively driving leukemogenesis in T-ALL."},"narrative":{"mechanistic_narrative":"RPL10 (QM/uL16) is an essential protein of the 60S large ribosomal subunit that couples late cytoplasmic ribosome maturation to the mechanics of translation elongation [PMID:18824477, PMID:24214990]. It assembles onto the 60S subunit at a late cytoplasmic step rather than in the nucleolus [PMID:9443083], where it is required for release of the nuclear export adapter Nmd3 from the ribosome; mutations in its central loop (residues ~102–112) impair Nmd3 release, and the loop also mediates recruitment of the maturation factor Sdo1, linking maturation to the subunit's rotational state [PMID:17761675, PMID:24214990]. Within the mature ribosome, an internal loop of RPL10 acts as a central controller of intersubunit rotation that propagates allosteric information across both subunits, while its N-terminal hook inserts into 25S/23S rRNA helix 89 to govern tRNA movement through the large subunit and translational fidelity [PMID:18824477, PMID:24214990]; the bacterial ortholog uL16 participates in A-tRNA discrimination at the A-site entrance corridor [PMID:27791159]. In bacteria, the L10 ortholog autoregulates its own operon by forming an L10(L12)4 complex that binds kink-turn motifs shared between its mRNA leader and rRNA, repressing expression by translational or transcription-attenuation mechanisms, and free L10 is rapidly degraded unless stabilized by L12 [PMID:6765237, PMID:18247578, PMID:26101249, PMID:2403546]. Beyond the ribosome, RPL10 binds the SH3 domain of c-Yes and suppresses its kinase activity [PMID:12138090], localizes to mitochondria where it modulates Complex I activity and ROS levels [PMID:30172100], and undergoes ufmylation that drives cancer cell proliferation and stemness via KLF4 [PMID:37280198]. Recurrent somatic RPL10 mutations, most notably R98S, occur in ~10% of pediatric T-ALL and cause ribosome biogenesis defects [PMID:23263491]; mechanistically R98S traps Nmd3 in the P site by blocking Sdo1-stimulated Efl1 GTPase activity [PMID:28715419], impairs programmed ribosomal frameshifting at JAK-STAT genes to hyper-activate that pathway [PMID:28744013], and shifts cells toward IRES-dependent BCL-2 translation under mitochondrial ROS stress, conferring Venetoclax sensitivity [PMID:29930300]. RPL10 missense variants also cause X-linked microcephaly and intellectual disability with associated translational defects [PMID:25316788, PMID:26290468].","teleology":[{"year":1980,"claim":"Established that the L10 ribosomal protein controls its own expression, defining ribosomal protein autoregulation at the translational level.","evidence":"DNA-dependent cell-free in vitro translation with purified E. coli L10","pmids":["6994102"],"confidence":"High","gaps":["Did not identify the RNA element bound","Bacterial system; eukaryotic relevance untested"]},{"year":1982,"claim":"Identified the molecular basis of autoregulation by showing the L10-L12 complex binds the operon mRNA leader and that rRNA competes for binding, providing a feedback link between ribosome assembly and protein synthesis.","evidence":"mRNA binding assays, leader RNA deletion/point mutations, rRNA competition","pmids":["6765237"],"confidence":"High","gaps":["Structural basis of dual mRNA/rRNA recognition not resolved","Bacterial operon context"]},{"year":1990,"claim":"Resolved how L10/L12 stoichiometry is balanced, showing free L10 is degraded unless stabilized by complex formation with L7/L12.","evidence":"rplL ribosome-binding-site genetics, overproduction, pulse-chase stability analysis in E. coli","pmids":["2403546"],"confidence":"Medium","gaps":["Protease responsible not identified","Bacterial system"]},{"year":1996,"claim":"Connected mammalian RPL10 to candidate extraribosomal roles by identifying it as the Jun-binding protein/QM tumor-suppressor homolog.","evidence":"cDNA and N-terminal protein sequencing, Southern blot","pmids":["8780716"],"confidence":"Medium","gaps":["Functional consequence of Jun interaction not tested here"]},{"year":1998,"claim":"Localized 60S assembly of RPL10 to the cytoplasm, establishing that it acts at a late, post-nucleolar maturation step.","evidence":"Immunofluorescence co-localization with a core 60S protein in human cells","pmids":["9443083"],"confidence":"Medium","gaps":["Single localization method","Mechanism of assembly not defined"]},{"year":2002,"claim":"Provided direct biochemical evidence for an extraribosomal signaling role by showing RPL10/QM binds and suppresses c-Yes kinase.","evidence":"SH3 pull-down/co-IP, in vitro kinase and autophosphorylation assays, immunofluorescence","pmids":["12138090"],"confidence":"Medium","gaps":["Physiological context of c-Yes suppression unclear","Single lab"]},{"year":2007,"claim":"Mapped a central loop of Rpl10 as required for release of the export adapter Nmd3, linking RPL10 to controlled 60S maturation and nuclear export.","evidence":"Systematic mutagenesis, Nmd3 release and localization assays in yeast","pmids":["17761675"],"confidence":"High","gaps":["Structural state of the loop during release not captured","GTPase coupling not yet defined"]},{"year":2008,"claim":"Defined how RPL10 transduces conformational signals, showing the N-terminal hook in rRNA helix 89 controls tRNA movement, elongation factor binding, and fidelity.","evidence":"Yeast mutagenesis, rRNA chemical probing, drug-sensitivity and fidelity assays","pmids":["18824477"],"confidence":"High","gaps":["Atomic-resolution dynamics of the hook during elongation not resolved"]},{"year":2008,"claim":"Showed the L10(L12)4 complex uses shared kink-turn motifs to bind both mRNA and rRNA, unifying the autoregulatory and assembly functions, with L11 enhancing rRNA binding.","evidence":"Fluorescence binding/affinity assays and kink-turn mutagenesis with bacterial L10(L12)4","pmids":["18247578"],"confidence":"High","gaps":["Bacterial system","Eukaryotic equivalent of motif-based regulation untested"]},{"year":2013,"claim":"Identified the RPL10 internal loop as a central controller of ribosomal intersubunit rotation that allosterically links all functional centers and couples rotation to Sdo1-dependent maturation.","evidence":"rRNA chemical probing, frameshifting/fidelity assays, suppressor genetics, EF-binding assays in yeast","pmids":["24214990"],"confidence":"High","gaps":["Direct structural snapshots of loop-driven rotation lacking"]},{"year":2012,"claim":"Linked RPL10 to cancer by discovering recurrent somatic mutations (R98S) in pediatric T-ALL associated with ribosome biogenesis defects.","evidence":"Exome sequencing of T-ALL patients with yeast and lymphoid cell functional validation","pmids":["23263491"],"confidence":"Medium","gaps":["Molecular mechanism of R98S not yet defined at this stage"]},{"year":2017,"claim":"Defined the molecular defect of R98S, showing it traps Nmd3 in the P site by blocking Sdo1-stimulated Efl1 GTPase activity, with suppressors validating the mechanism.","evidence":"In vitro reconstitution with purified components, GTPase and Nmd3 release assays, yeast suppressor genetics","pmids":["28715419"],"confidence":"High","gaps":["How trapped Nmd3 translates to oncogenic ribosome function not addressed here"]},{"year":2017,"claim":"Connected R98S to oncogenic signaling, showing impaired ribosomal frameshifting at JAK-STAT genes reduces JAK1 degradation and hyper-activates JAK-STAT.","evidence":"Proteome screen, transgenic mouse and xenograft models, frameshift reporters, proteasome assays","pmids":["28744013"],"confidence":"High","gaps":["Generality of frameshift defect across transcripts not fully mapped"]},{"year":2018,"claim":"Established a metabolic/survival axis for R98S, linking ROS accumulation and mitochondrial dysfunction to IRES-driven BCL-2 translation and Venetoclax sensitivity.","evidence":"ROS/mitochondrial/ATP assays, IRES reporters, BCL-2 quantification, xenograft Venetoclax treatment","pmids":["29930300"],"confidence":"High","gaps":["Mechanism coupling ribosome defect to IRES selectivity not fully resolved"]},{"year":2018,"claim":"Identified a mitochondrial role for RPL10 in regulating Complex I activity and ROS, while excluding a transcription-factor function.","evidence":"ChIP-seq, transcriptomics, Complex I activity and ROS assays in pancreatic cancer cells","pmids":["30172100"],"confidence":"Medium","gaps":["How a ribosomal protein localizes to and acts in mitochondria unresolved","Single lab"]},{"year":2014,"claim":"Demonstrated RPL10 dosage and loss-of-function cause neurodevelopmental disease, with K78E reducing bulk translation and increasing brain apoptosis.","evidence":"Zebrafish knockdown and in vivo complementation, translation and apoptosis assays","pmids":["25316788"],"confidence":"High","gaps":["Tissue specificity of translational vulnerability not explained"]},{"year":2023,"claim":"Identified ufmylation of RPL10 as a post-translational modification driving cancer cell proliferation and stemness via KLF4 upregulation.","evidence":"Mass spectrometry site mapping, site mutagenesis, proliferation/stemness assays, KLF4 analysis in tissues","pmids":["37280198"],"confidence":"Medium","gaps":["UFM1 ligase machinery and mechanistic link to KLF4 not defined","Single lab"]},{"year":null,"claim":"How RPL10's ribosomal, mitochondrial, and signaling activities are integrated, and how its ufmylation and extraribosomal interactions are regulated in human cells, remains open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of human RPL10 during Nmd3 release","Mechanism of mitochondrial targeting unknown","Regulation of ufmylation in vivo undefined"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[13,16,17]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,14,20]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[12,16,22]}],"localization":[{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[6,13,21]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[6]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[25]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[12,22]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[15,23,24]}],"complexes":["60S large ribosomal subunit","L10(L12)4 complex"],"partners":["NMD3","EFL1","SBDS","RPL12","YES1","RPL11","UFM1","RPS6"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P27635","full_name":"Large ribosomal subunit protein uL16","aliases":["60S ribosomal protein L10","Laminin receptor homolog","Protein QM","Ribosomal protein L10","Tumor suppressor QM"],"length_aa":214,"mass_kda":24.6,"function":"Component of the large ribosomal subunit (PubMed:26290468). Plays a role in the formation of actively translating ribosomes (PubMed:26290468). 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biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/25761118","citation_count":22,"is_preprint":false},{"pmid":"22468692","id":"PMC_22468692","title":"Identification and expression of small non-coding RNA, L10-Leader, in different growth phases of Streptococcus mutans.","date":"2012","source":"Nucleic acid therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/22468692","citation_count":22,"is_preprint":false},{"pmid":"16342232","id":"PMC_16342232","title":"Expression of the NKG2D ligand UL16 binding protein-1 (ULBP-1) on dendritic cells.","date":"2006","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/16342232","citation_count":21,"is_preprint":false},{"pmid":"10234813","id":"PMC_10234813","title":"Analysis of the pattern of QM expression during mouse development.","date":"1999","source":"Differentiation; research in biological diversity","url":"https://pubmed.ncbi.nlm.nih.gov/10234813","citation_count":21,"is_preprint":false},{"pmid":"28275195","id":"PMC_28275195","title":"The Product of the Herpes Simplex Virus 2 UL16 Gene Is Critical for the Egress of Capsids from the Nuclei of Infected Cells.","date":"2017","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/28275195","citation_count":21,"is_preprint":false},{"pmid":"29066376","id":"PMC_29066376","title":"A de novo mutation in RPL10 causes a rare X-linked ribosomopathy characterized by syndromic intellectual disability and epilepsy: A new case and review of the literature.","date":"2017","source":"European journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/29066376","citation_count":19,"is_preprint":false},{"pmid":"28715419","id":"PMC_28715419","title":"The T-cell leukemia related rpl10-R98S mutant traps the 60S export adapter Nmd3 in the ribosomal P site in yeast.","date":"2017","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28715419","citation_count":19,"is_preprint":false},{"pmid":"27791159","id":"PMC_27791159","title":"Avilamycin and evernimicin induce structural changes in rProteins uL16 and CTC that enhance the inhibition of A-site tRNA binding.","date":"2016","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/27791159","citation_count":19,"is_preprint":false},{"pmid":"2403546","id":"PMC_2403546","title":"Escherichia coli ribosomal protein L10 is rapidly degraded when synthesized in excess of ribosomal protein L7/L12.","date":"1990","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/2403546","citation_count":19,"is_preprint":false},{"pmid":"35226489","id":"PMC_35226489","title":"Factors That Determine the Variation of Equilibrium and Kinetic Properties of QM/MM Enzyme Simulations: QM Region, Conformation, and Boundary Condition.","date":"2022","source":"Journal of chemical theory and computation","url":"https://pubmed.ncbi.nlm.nih.gov/35226489","citation_count":19,"is_preprint":false},{"pmid":"31092572","id":"PMC_31092572","title":"Differential Requirements for gE, gI, and UL16 among Herpes Simplex Virus 1 Syncytial Variants Suggest Unique Modes of Dysregulating the Mechanism of Cell-to-Cell Spread.","date":"2019","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/31092572","citation_count":18,"is_preprint":false},{"pmid":"30465930","id":"PMC_30465930","title":"Glycoprotein D of HSV-1 is dependent on tegument protein UL16 for packaging and contains a motif that is differentially required for syncytia formation.","date":"2018","source":"Virology","url":"https://pubmed.ncbi.nlm.nih.gov/30465930","citation_count":17,"is_preprint":false},{"pmid":"16079476","id":"PMC_16079476","title":"Overexpression of QM induces cell differentiation and mineralization in MC3T3-E1.","date":"2005","source":"Biological & pharmaceutical bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/16079476","citation_count":17,"is_preprint":false},{"pmid":"26101249","id":"PMC_26101249","title":"Ribosomal protein L10(L12)4 autoregulates expression of the Bacillus subtilis rplJL operon by a transcription attenuation mechanism.","date":"2015","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/26101249","citation_count":17,"is_preprint":false},{"pmid":"31062376","id":"PMC_31062376","title":"QM/MM study of the taxadiene synthase mechanism.","date":"2019","source":"Journal of computational chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31062376","citation_count":17,"is_preprint":false},{"pmid":"28115505","id":"PMC_28115505","title":"Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4+ T Cells.","date":"2017","source":"Infection and immunity","url":"https://pubmed.ncbi.nlm.nih.gov/28115505","citation_count":17,"is_preprint":false},{"pmid":"16548884","id":"PMC_16548884","title":"The human cytomegalovirus glycoprotein UL16 traffics through the plasma membrane and the nuclear envelope.","date":"2006","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/16548884","citation_count":17,"is_preprint":false},{"pmid":"23034747","id":"PMC_23034747","title":"QM and QM/MM simulations of proteins.","date":"2013","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/23034747","citation_count":15,"is_preprint":false},{"pmid":"27847362","id":"PMC_27847362","title":"Domain Interaction Studies of Herpes Simplex Virus 1 Tegument Protein UL16 Reveal Its Interaction with Mitochondria.","date":"2017","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/27847362","citation_count":15,"is_preprint":false},{"pmid":"34978450","id":"PMC_34978450","title":"Predicting Effects of Site-Directed Mutagenesis on Enzyme Kinetics by QM/MM and QM Calculations: A Case of Glutamate Carboxypeptidase II.","date":"2022","source":"The journal of physical chemistry. B","url":"https://pubmed.ncbi.nlm.nih.gov/34978450","citation_count":15,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":45838,"output_tokens":6702,"usd":0.119022,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":15763,"output_tokens":4681,"usd":0.09792,"stage2_stop_reason":"end_turn"},"total_usd":0.216942,"stage1_batch_id":"msgbatch_01CNoDbkChHEkgrJnL7BwtGJ","stage2_batch_id":"msgbatch_016Y4x9E9Wg5VQDANj9quSQD","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1982,\n      \"finding\": \"The ribosomal protein L10-L12 complex binds specifically to the leader sequence of the L10 operon mRNA, preventing translation of L10 and L12 proteins. rRNA prevents this binding, and extended sequence homologies between 23S rRNA and the L10 leader RNA were identified, suggesting the L10-L12 complex can be sequestered into assembling 50S subunits to relieve translational repression.\",\n      \"method\": \"mRNA binding assay, deletion/point mutation analysis of leader RNA, rRNA competition assay\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal in vitro binding and mutational analyses; replicated by independent work (PMID:6994102, PMID:379826)\",\n      \"pmids\": [\"6765237\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1980,\n      \"finding\": \"E. coli ribosomal protein L10 autoregulates its own translation in vitro: addition of exogenous L10 inhibits L10 synthesis but not L12, beta/beta'-RNA polymerase subunit, or EF-Tu synthesis. Inhibition occurs at the level of translation, not mRNA degradation.\",\n      \"method\": \"DNA-dependent cell-free protein synthesis (in vitro translation assay) with purified L10\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct in vitro reconstitution assay showing autogenous translational repression, consistent with PMID:6765237\",\n      \"pmids\": [\"6994102\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1979,\n      \"finding\": \"Chemical modification of arginine residues in E. coli ribosomal protein L10 inhibits its binding to ribosomes and 23S rRNA but does not affect its ability to bind four molecules of L7/L12. This suggests L10 uses separate domains for rRNA/ribosome binding versus L7/L12 interaction, and its role in promoting L7/L12 ribosome association is mediated through simultaneous binding to both 23S rRNA and L7/L12.\",\n      \"method\": \"Chemical modification (arginine-specific reagents) of L10 followed by binding assays with ribosomes, 23S rRNA, and L7/L12\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — chemical modification plus multiple binding assays in single study; single lab\",\n      \"pmids\": [\"379826\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1989,\n      \"finding\": \"Structural and sequence analysis revealed that eukaryotic and archaebacterial L10 proteins contain approximately three-fourths of an L12 protein sequence fused to their C-terminus, with a repeated 26-amino acid module present in two copies in eukaryotes that may mediate L12 dimerization and L10-L12 complex formation.\",\n      \"method\": \"Comparative sequence analysis of cloned L10 genes from Halobacterium, Sulfolobus, and Saccharomyces cerevisiae\",\n      \"journal\": \"Canadian journal of microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/sequence analysis only, no direct functional experiment\",\n      \"pmids\": [\"2497941\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1990,\n      \"finding\": \"E. coli ribosomal protein L10 is rapidly proteolytically degraded when synthesized in excess of L7/L12. L7/L12 stabilizes L10 by forming a complex with it; free L10 (not complexed with L7/L12) is subject to rapid proteolytic decay, contributing to balanced stoichiometric expression of both proteins.\",\n      \"method\": \"Genetic manipulation of rplL ribosome-binding site, overproduction in trans, pulse-chase analysis of protein stability\",\n      \"journal\": \"Journal of bacteriology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo genetic and biochemical experiments demonstrating proteolytic regulation; single lab\",\n      \"pmids\": [\"2403546\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"Rat ribosomal protein L10 was found to be the mammalian homolog of the chicken Jun-binding protein (Jif-1) and nearly identical to a putative Wilms' tumor suppressor (QM), indicating conservation of potential extraribosomal functions. The protein has 213 amino acids (N-terminal Met removed post-translationally) with a molecular weight of 24,456 Da.\",\n      \"method\": \"cDNA sequencing, N-terminal amino acid sequencing, Southern blot hybridization\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct protein sequencing and molecular characterization; single lab\",\n      \"pmids\": [\"8780716\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"The human QM protein (RPL10) assembles onto the 60S ribosomal subunit in the cytoplasm, not in the nucleolus. Immunofluorescence co-localization showed QM co-localizes with the large P-antigen (60S core ribosomal protein) only in the cytoplasm at the rough endoplasmic reticulum, consistent with a role in a late step of 60S subunit assembly.\",\n      \"method\": \"Indirect immunofluorescence co-localization with core 60S ribosomal protein (large P-antigen) in human cells\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional interpretation; single lab, one orthogonal method\",\n      \"pmids\": [\"9443083\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"The QM protein (RPL10) interacts with the SH3 domain of the proto-oncogene c-Yes kinase through two distinct regions of QM (neither containing canonical SH3 binding motifs), reduces c-Yes kinase activity by ~70%, and inhibits c-Yes autophosphorylation. QM overexpression also increases c-Yes protein and mRNA levels. Co-localization in tumor cell lines was demonstrated by immunofluorescence.\",\n      \"method\": \"SH3 domain pull-down/co-IP, in vitro kinase activity assay, autophosphorylation assay, immunofluorescence co-localization\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple in vitro assays plus cell-based co-localization; single lab\",\n      \"pmids\": [\"12138090\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"E. histolytica L10 (EhL10, homologous to human QM/RPL10) is part of the ribosomal complex, localizes primarily to the nucleus of trophozoites, and overexpression reduces cellular growth by 60%. DNA mobility-shift assays showed EhL10 can destabilize the AP-1 (activating protein 1) complex by binding specifically to the c-Jun-like protein, suggesting an extraribosomal function in suppressing c-Jun-dependent gene transcription.\",\n      \"method\": \"Western blot fractionation, immunofluorescence, overexpression growth assay, DNA mobility-shift (EMSA) assay\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — multiple assays in parasite model orthologous to human RPL10; single lab\",\n      \"pmids\": [\"12672524\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"In yeast, rpL10/Grc5p functionally interacts with the nuclear export factor Nmd3p to modulate the cellular polysome complement, and with small subunit protein rpS6 in 40S/60S subunit joining and differential protein expression.\",\n      \"method\": \"Genetic and biochemical analysis of polysome profiles, subunit joining assays, functional interaction studies in S. cerevisiae\",\n      \"journal\": \"FEMS yeast research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple functional assays in yeast model; single lab\",\n      \"pmids\": [\"15556089\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Two missense mutations (L206M and H213Q) in human RPL10 identified in autism patients confer hypomorphism with respect to translational regulation while preserving basic translation function, as assessed using yeast as a model system with aberrant ribosomal profiles.\",\n      \"method\": \"Yeast complementation/ribosomal profile analysis with patient-derived RPL10 mutants\",\n      \"journal\": \"Molecular psychiatry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional yeast assay with disease mutants showing ribosomal profiling defects; single lab\",\n      \"pmids\": [\"16940977\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Heterozygosity for rpl10Δ in yeast reduces the translating ribosome population and increases replicative lifespan by 24%, linking RPL10 gene dosage to modulation of translation and aging.\",\n      \"method\": \"Yeast deletion genetics, polysome profiling, replicative lifespan assay\",\n      \"journal\": \"Experimental gerontology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct genetic experiment with multiple readouts in yeast; single lab\",\n      \"pmids\": [\"17174052\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Extensive mutational analysis of yeast Rpl10 showed that mutations in a central loop (residues 102–112) significantly impair release of the 60S nuclear export adapter Nmd3, while Rpl10 mutants unable to bind the ribosome accumulate in the nucleus, suggesting a nuclear role. The central loop is unstructured in prokaryotic crystal/solution structures and plays a dynamic role in ribosome function or factor regulation.\",\n      \"method\": \"Systematic mutagenesis of RPL10, Nmd3 release assays, subcellular localization analysis in S. cerevisiae\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — extensive mutational analysis with multiple functional readouts; domain mapping consistent with structural data\",\n      \"pmids\": [\"17761675\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Yeast ribosomal protein L10's N-terminal 'hook' (which inserts into 25S rRNA helix 89 bulge) controls tRNA movement through the large subunit. Mutations in this domain cause broad effects on rRNA structure along the tRNA 3' end path, ribosome biogenesis, elongation factor binding, drug resistance, and translational fidelity, indicating L10 transduces conformational information through the ribosome.\",\n      \"method\": \"Yeast mutagenesis, killer virus maintenance assay (proxy for 60S defects), rRNA chemical modification (SHAPE/DMS), drug sensitivity, translational fidelity assays\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal biochemical and genetic assays; rRNA structural probing plus functional analyses\",\n      \"pmids\": [\"18824477\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"The L10(L12)4 pentameric complex binds both mRNA leader and rRNA targets using structurally similar kink-turn RNA motifs. The ribosomal protein L11 enhances L10(L12)4 binding to rRNA by ~100-fold through a protein-protein interaction, ensuring saturation of the ribosomal binding site. mRNA and rRNA targets use equivalent kink-turn and loop-AA recognition elements but in different structural contexts.\",\n      \"method\": \"Fluorescence binding assays, mutagenesis of kink-turn motifs in mRNA and rRNA, quantitative affinity measurements using Bacillus stearothermophilus L10(L12)4\",\n      \"journal\": \"Biochemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — quantitative binding assays, mutagenesis, fluorescence methods; multiple orthogonal approaches in single rigorous study\",\n      \"pmids\": [\"18247578\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Recurrent somatic mutations in RPL10 (most notably Arg98Ser, R98S) are found in ~10% of pediatric T-ALL patients. Yeast and lymphoid cells expressing RPL10 R98S showed a ribosome biogenesis defect.\",\n      \"method\": \"Exome sequencing of T-ALL patients, functional validation in yeast and lymphoid cells (ribosomal profiling)\",\n      \"journal\": \"Nature genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — patient mutation discovery plus functional ribosome biogenesis assay; replicated in two model systems\",\n      \"pmids\": [\"23263491\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"An internal loop in yeast rpL10 acts as a central controller of ribosomal intersubunit rotation. Mutations in this loop cause opposing shifts in the rotational equilibrium between non-rotated and rotated ribosomal states, with allosteric effects propagating through both subunits and linking all functional centers. An rpL3 mutation with opposing structural effects suppresses an rpL10 mutant by re-establishing rotational equilibrium. The rpL10 loop is also involved in Sdo1p recruitment, linking rotational status to late-stage 60S maturation.\",\n      \"method\": \"rRNA chemical modification (DMS), ribosomal frameshifting assays, translational fidelity assays, genetic suppressor analysis, biochemical elongation factor binding assays in S. cerevisiae\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — multiple orthogonal methods (chemical probing, genetics, biochemistry, fidelity assays) in single comprehensive study; suppressor genetics validate mechanism\",\n      \"pmids\": [\"24214990\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"A novel RPL10 missense mutation (p.K78E) causes X-linked microcephaly with seizures and growth retardation. Zebrafish rpl10 knockdown decreases head size with reduced bulk translation and increased apoptosis in the brain. In vivo complementation showed p.K78E is a loss-of-function variant. RPL10 is in close proximity to the peptidyl transferase active site of the 60S subunit.\",\n      \"method\": \"Zebrafish morpholino knockdown, bulk translation assays, apoptosis assays, in vivo complementation with wildtype vs mutant RPL10\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal functional assays in zebrafish model with rescue experiment; direct loss-of-function phenotype linked to translation\",\n      \"pmids\": [\"25316788\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The antituberculosis antibiotic capreomycin inhibits the L12-L10 protein-protein interaction, thereby inhibiting elongation factor G-dependent GTPase activity and ribosome-mediated protein synthesis. Overexpression of L12 and/or L10 increases capreomycin MIC, and blocking protein synthesis with thiostrepton restrains capreomycin bactericidal activity.\",\n      \"method\": \"L12-L10 interaction assay, MIC measurements, in vitro GTPase activity assay, in vitro protein synthesis assay\",\n      \"journal\": \"Antimicrobial agents and chemotherapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple biochemical assays; bacterial L10 ortholog; single lab\",\n      \"pmids\": [\"24449778\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"A novel RPL10 missense mutation (p.A64V) in the N-terminal domain causes X-linked intellectual disability with cerebellar hypoplasia and spondylo-epiphyseal dysplasia. Unlike other RPL10 mutations, the A64V variant generates a functional ribosomal protein able to complement yeast translational defects but results in an increase in the actively translating ribosome population.\",\n      \"method\": \"Yeast complementation assay, polysome profiling, translational capacity measurement\",\n      \"journal\": \"Human mutation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — yeast functional assays showing gain-of-translation phenotype; single lab\",\n      \"pmids\": [\"26290468\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"In Bacillus subtilis, the ribosomal protein L10(L12)4 complex autoregulates rplJL operon expression by a transcription attenuation mechanism: L10(L12)4 binds to an anti-antiterminator RNA structure in the rplJL leader transcript, stabilizing it and promoting formation of an intrinsic terminator, thereby repressing transcription. This is distinct from the E. coli translational repression mechanism.\",\n      \"method\": \"Transcriptional and translational fusions, RNA binding studies, in vitro transcription, competitor oligonucleotides, in vivo mutational analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro transcription, RNA binding, and multiple in vivo mutational validations; multiple orthogonal methods in single study\",\n      \"pmids\": [\"26101249\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Crystal structures of the eubacterial large ribosomal subunit in complex with orthosomycin antibiotics (avilamycin and evernimicin) revealed that ribosomal protein uL16 (RPL10 bacterial ortholog) participates in binding and discriminating A-tRNA at the A-tRNA entrance corridor. Structural analysis showed that differences in the α1 helix length of uL16 between eukaryotes and prokaryotes are key determinants of drug selectivity.\",\n      \"method\": \"High-resolution X-ray crystallography of large ribosomal subunit–antibiotic complexes\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution crystal structures providing mechanistic detail about uL16 role in A-tRNA discrimination and antibiotic selectivity\",\n      \"pmids\": [\"27791159\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The T-ALL-associated RPL10 R98S mutation causes failure to release the 60S export adapter Nmd3 from the ribosomal P site. In vitro reconstitution showed Nmd3 inhibits Sdo1-stimulated Efl1 GTPase activity on RPL10 R98S but not wild-type 60S subunits. Suppressor mutations in Nmd3 and Tif6 that disrupted Nmd3-ribosome or Nmd3-Tif6 interactions rescued the defect in vivo and in vitro, defining the molecular defect of RPL10 R98S.\",\n      \"method\": \"In vitro reconstitution with purified components, Nmd3 release assays, Efl1 GTPase activity assays, suppressor genetic screen, yeast genetics\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution with purified components plus in vivo genetic suppressor validation; multiple orthogonal approaches\",\n      \"pmids\": [\"28715419\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The RPL10 R98S mutation causes overexpression of JAK-STAT signaling proteins in mouse lymphoid cells. RPL10 R98S expressing cells display JAK-STAT pathway hyper-activation upon cytokine stimulation. Mechanistically, RPL10 R98S reduces apparent programmed ribosomal frameshifting at JAK-STAT gene frameshift signals and decreases JAK1 degradation. RPL10 R98S cells also show reduced proteasome activity.\",\n      \"method\": \"Proteome screen, transgenic mouse model, xenograft T-ALL samples, cytokine stimulation assays, ribosomal frameshift reporter assays, proteasome activity assays\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods across mouse model, human xenograft, and cell-based systems; multiple labs contribute validation\",\n      \"pmids\": [\"28744013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"RPL10 R98S mutant leukemia cells accumulate reactive oxygen species, causing mitochondrial dysfunction and reduced ATP levels, leading to a proliferation defect. These cells survive oxidative stress via specific upregulation of IRES-mediated translation of BCL-2 anti-apoptotic factor, resulting in BCL-2 protein overexpression and sensitivity to the BCL-2 inhibitor Venetoclax.\",\n      \"method\": \"ROS measurement, mitochondrial function assays, ATP quantification, IRES reporter assays, BCL-2 protein quantification, xenograft mouse model with Venetoclax treatment\",\n      \"journal\": \"Leukemia\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal mechanistic assays plus in vivo xenograft validation; novel mechanism defined by IRES reporter and ROS measurements\",\n      \"pmids\": [\"29930300\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"RPL10 in mitochondria of pancreatic cancer cells regulates ROS levels by affecting mitochondrial Complex I activity. ChIP-seq showed RPL10 is unlikely to function as a transcription factor. Transcriptome analysis indicated RPL10 regulates expression of proteins related to ROS production.\",\n      \"method\": \"Chromatin immunoprecipitation sequencing (ChIP-seq), transcriptome analysis, mitochondrial Complex I activity assay, ROS measurement\",\n      \"journal\": \"Redox biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical assay of Complex I activity plus ChIP-seq; single lab, mechanistic follow-up limited\",\n      \"pmids\": [\"30172100\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"RPL10 undergoes ufmylation (UFM1 modification) in pancreatic cancer tissues and cell lines, with specific modification sites identified and verified by mutagenesis. RPL10 ufmylation increases cell proliferation and stemness primarily through upregulation of the transcription factor KLF4. Mutagenesis of ufmylation sites in RPL10 confirmed the connection between ufmylation and these cellular phenotypes.\",\n      \"method\": \"Mass spectrometry identification of ufmylation sites, site-directed mutagenesis, cell proliferation assays, stemness assays, KLF4 expression analysis in patient tissues and cell lines\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — PTM site identification plus mutagenesis validation with cellular readouts; single lab\",\n      \"pmids\": [\"37280198\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPL10 (QM/uL16) is an essential component of the 60S large ribosomal subunit that acts as a central regulator of ribosome function: its internal loop controls intersubunit rotation and drives the elongation cycle, its N-terminal hook coordinates tRNA movement through the large subunit, and it is required at a late cytoplasmic step for 60S maturation by enabling release of the export adapter Nmd3 (via Sdo1-stimulated Efl1 GTPase activity) and facilitating joining with the 40S subunit; beyond its ribosomal role, RPL10 autoregulates its own synthesis by forming an L10-L12 complex that binds the mRNA leader to repress translation, is stabilized by complex formation with L12 (free L10 is rapidly degraded), can suppress c-Yes kinase activity through direct SH3 domain interaction, and undergoes ufmylation that promotes cancer cell stemness; oncogenic mutations such as R98S trap Nmd3 in the P site, impair programmed ribosomal frameshifting at JAK-STAT genes, enhance IRES-dependent BCL-2 translation, and accumulate ROS via mitochondrial Complex I, collectively driving leukemogenesis in T-ALL.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPL10 (QM/uL16) is an essential protein of the 60S large ribosomal subunit that couples late cytoplasmic ribosome maturation to the mechanics of translation elongation [#13, #16]. It assembles onto the 60S subunit at a late cytoplasmic step rather than in the nucleolus [#6], where it is required for release of the nuclear export adapter Nmd3 from the ribosome; mutations in its central loop (residues ~102–112) impair Nmd3 release, and the loop also mediates recruitment of the maturation factor Sdo1, linking maturation to the subunit's rotational state [#12, #16]. Within the mature ribosome, an internal loop of RPL10 acts as a central controller of intersubunit rotation that propagates allosteric information across both subunits, while its N-terminal hook inserts into 25S/23S rRNA helix 89 to govern tRNA movement through the large subunit and translational fidelity [#13, #16]; the bacterial ortholog uL16 participates in A-tRNA discrimination at the A-site entrance corridor [#21]. In bacteria, the L10 ortholog autoregulates its own operon by forming an L10(L12)4 complex that binds kink-turn motifs shared between its mRNA leader and rRNA, repressing expression by translational or transcription-attenuation mechanisms, and free L10 is rapidly degraded unless stabilized by L12 [#0, #14, #20, #4]. Beyond the ribosome, RPL10 binds the SH3 domain of c-Yes and suppresses its kinase activity [#7], localizes to mitochondria where it modulates Complex I activity and ROS levels [#25], and undergoes ufmylation that drives cancer cell proliferation and stemness via KLF4 [#26]. Recurrent somatic RPL10 mutations, most notably R98S, occur in ~10% of pediatric T-ALL and cause ribosome biogenesis defects [#15]; mechanistically R98S traps Nmd3 in the P site by blocking Sdo1-stimulated Efl1 GTPase activity [#22], impairs programmed ribosomal frameshifting at JAK-STAT genes to hyper-activate that pathway [#23], and shifts cells toward IRES-dependent BCL-2 translation under mitochondrial ROS stress, conferring Venetoclax sensitivity [#24]. RPL10 missense variants also cause X-linked microcephaly and intellectual disability with associated translational defects [#17, #19].\"\n,\n  \"teleology\": [\n    {\n      \"year\": 1980,\n      \"claim\": \"Established that the L10 ribosomal protein controls its own expression, defining ribosomal protein autoregulation at the translational level.\",\n      \"evidence\": \"DNA-dependent cell-free in vitro translation with purified E. coli L10\",\n      \"pmids\": [\"6994102\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify the RNA element bound\", \"Bacterial system; eukaryotic relevance untested\"]\n    },\n    {\n      \"year\": 1982,\n      \"claim\": \"Identified the molecular basis of autoregulation by showing the L10-L12 complex binds the operon mRNA leader and that rRNA competes for binding, providing a feedback link between ribosome assembly and protein synthesis.\",\n      \"evidence\": \"mRNA binding assays, leader RNA deletion/point mutations, rRNA competition\",\n      \"pmids\": [\"6765237\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of dual mRNA/rRNA recognition not resolved\", \"Bacterial operon context\"]\n    },\n    {\n      \"year\": 1990,\n      \"claim\": \"Resolved how L10/L12 stoichiometry is balanced, showing free L10 is degraded unless stabilized by complex formation with L7/L12.\",\n      \"evidence\": \"rplL ribosome-binding-site genetics, overproduction, pulse-chase stability analysis in E. coli\",\n      \"pmids\": [\"2403546\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Protease responsible not identified\", \"Bacterial system\"]\n    },\n    {\n      \"year\": 1996,\n      \"claim\": \"Connected mammalian RPL10 to candidate extraribosomal roles by identifying it as the Jun-binding protein/QM tumor-suppressor homolog.\",\n      \"evidence\": \"cDNA and N-terminal protein sequencing, Southern blot\",\n      \"pmids\": [\"8780716\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of Jun interaction not tested here\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Localized 60S assembly of RPL10 to the cytoplasm, establishing that it acts at a late, post-nucleolar maturation step.\",\n      \"evidence\": \"Immunofluorescence co-localization with a core 60S protein in human cells\",\n      \"pmids\": [\"9443083\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single localization method\", \"Mechanism of assembly not defined\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Provided direct biochemical evidence for an extraribosomal signaling role by showing RPL10/QM binds and suppresses c-Yes kinase.\",\n      \"evidence\": \"SH3 pull-down/co-IP, in vitro kinase and autophosphorylation assays, immunofluorescence\",\n      \"pmids\": [\"12138090\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological context of c-Yes suppression unclear\", \"Single lab\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Mapped a central loop of Rpl10 as required for release of the export adapter Nmd3, linking RPL10 to controlled 60S maturation and nuclear export.\",\n      \"evidence\": \"Systematic mutagenesis, Nmd3 release and localization assays in yeast\",\n      \"pmids\": [\"17761675\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural state of the loop during release not captured\", \"GTPase coupling not yet defined\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Defined how RPL10 transduces conformational signals, showing the N-terminal hook in rRNA helix 89 controls tRNA movement, elongation factor binding, and fidelity.\",\n      \"evidence\": \"Yeast mutagenesis, rRNA chemical probing, drug-sensitivity and fidelity assays\",\n      \"pmids\": [\"18824477\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic-resolution dynamics of the hook during elongation not resolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Showed the L10(L12)4 complex uses shared kink-turn motifs to bind both mRNA and rRNA, unifying the autoregulatory and assembly functions, with L11 enhancing rRNA binding.\",\n      \"evidence\": \"Fluorescence binding/affinity assays and kink-turn mutagenesis with bacterial L10(L12)4\",\n      \"pmids\": [\"18247578\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Bacterial system\", \"Eukaryotic equivalent of motif-based regulation untested\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identified the RPL10 internal loop as a central controller of ribosomal intersubunit rotation that allosterically links all functional centers and couples rotation to Sdo1-dependent maturation.\",\n      \"evidence\": \"rRNA chemical probing, frameshifting/fidelity assays, suppressor genetics, EF-binding assays in yeast\",\n      \"pmids\": [\"24214990\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct structural snapshots of loop-driven rotation lacking\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Linked RPL10 to cancer by discovering recurrent somatic mutations (R98S) in pediatric T-ALL associated with ribosome biogenesis defects.\",\n      \"evidence\": \"Exome sequencing of T-ALL patients with yeast and lymphoid cell functional validation\",\n      \"pmids\": [\"23263491\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular mechanism of R98S not yet defined at this stage\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined the molecular defect of R98S, showing it traps Nmd3 in the P site by blocking Sdo1-stimulated Efl1 GTPase activity, with suppressors validating the mechanism.\",\n      \"evidence\": \"In vitro reconstitution with purified components, GTPase and Nmd3 release assays, yeast suppressor genetics\",\n      \"pmids\": [\"28715419\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How trapped Nmd3 translates to oncogenic ribosome function not addressed here\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Connected R98S to oncogenic signaling, showing impaired ribosomal frameshifting at JAK-STAT genes reduces JAK1 degradation and hyper-activates JAK-STAT.\",\n      \"evidence\": \"Proteome screen, transgenic mouse and xenograft models, frameshift reporters, proteasome assays\",\n      \"pmids\": [\"28744013\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Generality of frameshift defect across transcripts not fully mapped\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Established a metabolic/survival axis for R98S, linking ROS accumulation and mitochondrial dysfunction to IRES-driven BCL-2 translation and Venetoclax sensitivity.\",\n      \"evidence\": \"ROS/mitochondrial/ATP assays, IRES reporters, BCL-2 quantification, xenograft Venetoclax treatment\",\n      \"pmids\": [\"29930300\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism coupling ribosome defect to IRES selectivity not fully resolved\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identified a mitochondrial role for RPL10 in regulating Complex I activity and ROS, while excluding a transcription-factor function.\",\n      \"evidence\": \"ChIP-seq, transcriptomics, Complex I activity and ROS assays in pancreatic cancer cells\",\n      \"pmids\": [\"30172100\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How a ribosomal protein localizes to and acts in mitochondria unresolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrated RPL10 dosage and loss-of-function cause neurodevelopmental disease, with K78E reducing bulk translation and increasing brain apoptosis.\",\n      \"evidence\": \"Zebrafish knockdown and in vivo complementation, translation and apoptosis assays\",\n      \"pmids\": [\"25316788\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Tissue specificity of translational vulnerability not explained\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identified ufmylation of RPL10 as a post-translational modification driving cancer cell proliferation and stemness via KLF4 upregulation.\",\n      \"evidence\": \"Mass spectrometry site mapping, site mutagenesis, proliferation/stemness assays, KLF4 analysis in tissues\",\n      \"pmids\": [\"37280198\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"UFM1 ligase machinery and mechanistic link to KLF4 not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RPL10's ribosomal, mitochondrial, and signaling activities are integrated, and how its ufmylation and extraribosomal interactions are regulated in human cells, remains open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model of human RPL10 during Nmd3 release\", \"Mechanism of mitochondrial targeting unknown\", \"Regulation of ufmylation in vivo undefined\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [13, 16, 17]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 14, 20]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [12, 16, 22]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [6, 13, 21]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [25]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-72766\", \"supporting_discovery_ids\": [13, 16]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [12, 22]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [15, 23, 24]}\n    ],\n    \"complexes\": [\"60S large ribosomal subunit\", \"L10(L12)4 complex\"],\n    \"partners\": [\"NMD3\", \"EFL1\", \"SBDS\", \"RPL12\", \"YES1\", \"RPL11\", \"UFM1\", \"RPS6\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}