{"gene":"RPL14","run_date":"2026-06-10T06:43:37","timeline":{"discoveries":[{"year":1996,"finding":"Crystal structure of ribosomal protein L14 from Bacillus stearothermophilus was solved, revealing a five-stranded beta-barrel, a C-terminal loop region with two small alpha-helices, and a beta-ribbon projecting from the barrel. Analysis identified three surface patches likely mediating L14-RNA and L14-protein interactions, with two RNA-binding sites and a hydrophobic patch proposed as an L19 protein-protein interaction site.","method":"X-ray crystallography using isomorphous replacement and MAD methods, solved to high resolution","journal":"Structure (London, England : 1993)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure with functional surface analysis; single study but high-resolution structural determination with mutagenesis-guided interpretation","pmids":["8805509"],"is_preprint":false},{"year":1978,"finding":"Ribosomal protein L14 was purified from the 60S large ribosomal subunit of rat liver ribosomes, establishing it as a component of the eukaryotic 60S subunit with a defined molecular weight estimated by SDS-PAGE.","method":"Protein purification via ion-exchange chromatography (carboxymethylcellulose, DEAE-cellulose) and gel filtration; molecular weight by SDS-PAGE; amino acid composition analysis","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct biochemical isolation and characterization of the protein from native ribosomal subunits; foundational biochemistry paper","pmids":["621213"],"is_preprint":false},{"year":1978,"finding":"Ribosomal protein L14 in Krebs II ascites cells becomes phosphorylated when cells are incubated in Eagle's medium (glucose + amino acids), a condition that also causes dephosphorylation of Lgamma, suggesting that metabolic state regulates the pattern of ribosomal protein phosphorylation.","method":"Radiolabeled phosphorylation assays in Krebs II ascites cells under varying metabolic conditions; comparison of phosphorylation patterns on ribosomal proteins","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct phosphorylation detection in intact cells, single study, metabolic manipulation shows context-dependent modification","pmids":["27217"],"is_preprint":false},{"year":1989,"finding":"In E. coli, ribosomal protein S8 retroregulates synthesis of L14 and L24 (the first and second gene products of the spc operon) by acting at an mRNA target site distal to the L14/L24 coding sequences; mRNA degradation by 3'-to-5' exonucleases (polynucleotide phosphorylase and RNase II) is the mechanism of this retroregulation.","method":"Genetic analysis using single-base substitutions in the S8 target site; S8 overexpression in trans from a plasmid; temperature-sensitive mutations in polynucleotide phosphorylase and RNase II genes; differential synthesis rate measurements","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple genetic approaches (site mutations, overexpression, exonuclease-deficient strains) in a single rigorous study establishing retroregulation mechanism","pmids":["2643112"],"is_preprint":false},{"year":2006,"finding":"Compensatory evolution experiments in Salmonella typhimurium revealed that mutations in L14 can compensate for fitness costs of L19 mutations, demonstrating a functional interaction between L14 and L19 in the 50S subunit. L14 is located close to L19, and their interaction with 16S rRNA may influence 30S subunit function during the decoding step of translation.","method":"In vivo fitness measurements, serial passage for compensatory evolution, translation speed and accuracy assays (UGA read-through), aminoglycoside sensitivity testing, genetic epistasis","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal in vivo methods (fitness, accuracy, drug sensitivity) demonstrating functional L14-L19 interaction; replicated across multiple mutant backgrounds","pmids":["17157877"],"is_preprint":false},{"year":2018,"finding":"In Saccharomyces cerevisiae, L14 (eL14) assembles in the nucleolus at an early stage into pre-60S particles. Depletion of L14 causes defective processing of 27SA2 and 27SA3 to 27SB pre-rRNAs, leads to turnover of 27S pre-rRNAs, blocks export of pre-60S particles, and reduces association of neighboring ribosomal proteins at the solvent interface and around the polypeptide exit tunnel. Removal of the distal eukaryote-specific C-terminal extensions of L14 and L16 causes slight translation alterations in mature 60S subunits.","method":"Conditional depletion of L14; Northern blot analysis of pre-rRNA processing intermediates; sucrose gradient sedimentation; co-sedimentation of trans-acting factors; C-terminal truncation mutants analyzed for translation fidelity","journal":"Nucleic acids research","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional depletion with multiple orthogonal readouts (pre-rRNA processing, export, factor association, translation); rigorous yeast ribosome biogenesis study","pmids":["29788267"],"is_preprint":false},{"year":1997,"finding":"Haploinsufficiency of the Drosophila RPL14 gene (caused by a P-element insertion in the RPL14 promoter region) causes a strong Minute phenotype (short thin bristles, developmental delay, recessive lethality), establishing RPL14 as a dosage-sensitive ribosomal protein gene. Quantitative Northern blot showed reduction in RPL14 mRNA; remobilization of the P element restored wild-type RPL14 mRNA levels and normal phenotype.","method":"P-element mutagenesis; quantitative Northern blot; P-element remobilization rescue experiment; phenotypic analysis","journal":"Molecular & general genetics : MGG","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function with molecular confirmation and rescue experiment demonstrating causality","pmids":["9236770"],"is_preprint":false},{"year":2003,"finding":"Targeted RNA interference (RNAi) knockdown of Drosophila RpL14 using the GAL4/UAS system causes lethality and distinct somatic anomalies in both developing and differentiated cells, demonstrating that RPL14 is essential for normal cell proliferation and development when reduced below 50% of normal levels.","method":"Heritable RNAi via GAL4/UAS binary system; RNA-level confirmation of knockdown; phenotypic analysis of developing and differentiated tissues","journal":"Gene","confidence":"High","confidence_rationale":"Tier 2 / Moderate — spatiotemporal RNAi knockdown with RNA-level verification and defined phenotypic readouts; single lab but multiple tissue contexts examined","pmids":["14597387"],"is_preprint":false},{"year":1994,"finding":"The transcription factor FIII/YY1 (Xenopus homolog of human YY1/delta) binds to the first exon of the Xenopus laevis ribosomal protein L14 gene. The protein was identified to share antigenic and DNA-binding properties with the endogenous oocyte protein that contacts the first exon of rp genes L1 and L14.","method":"cDNA cloning; overexpression in Xenopus oocytes; immunological characterization; DNA-binding assays","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct binding demonstrated by DNA-binding assay and immunological cross-reactivity; single lab, single study","pmids":["7802655"],"is_preprint":false},{"year":1998,"finding":"FIII/YY1 binding sites in the first exon of Xenopus laevis RPL14 (and L1) promoters are dispensable for promoter expression: mutations in the FIII/YY1 sites did not change reporter (CAT) activity in oocyte injection assays or in transfected Xenopus kidney cells, and overexpression of FIII/YY1 had no effect.","method":"CAT reporter assays with wild-type and mutated FIII/YY1 binding sites; oocyte microinjection; cell transfection; FIII/YY1 overexpression","journal":"European journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — negative functional result established by two orthogonal cell systems (oocytes and kidney cells); single lab","pmids":["9738894"],"is_preprint":false},{"year":1996,"finding":"Human RPL14 (hRL14) encodes a 60S ribosomal subunit protein of 220 amino acids (predicted MW 23.6 kDa) containing nuclear targeting sequences, a bZIP-like element for rRNA binding, and internal pentapeptide repeat sequences. The COOH-terminal region contains 15 GCT (alanine) triplet repeats encoding a polyalanine tract.","method":"cDNA cloning and sequencing from human endothelial cell library; Northern blot analysis; bioinformatic domain analysis","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — primary structural characterization of the human protein with functional domain identification; no direct functional assays performed","pmids":["9480843"],"is_preprint":false},{"year":2025,"finding":"PRMT5 interacts with RPL14 and catalyzes symmetric dimethylation of RPL14 at arginine residues. This modification stabilizes RPL14 protein, promotes DNA damage repair (as measured by RAD51 expression), and contributes to regorafenib resistance in hepatocellular carcinoma cells. RPL14 knockdown increases DNA damage (γ-H2AX), reduces cell viability, and increases sensitivity to regorafenib.","method":"Mass spectrometry; co-immunoprecipitation; Western blot for γ-H2AX and RAD51; lentiviral PRMT5 overexpression; siRNA knockdown; immunofluorescence","journal":"Journal of gastrointestinal oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — interaction confirmed by mass spectrometry and Co-IP; functional consequence of dimethylation shown by multiple assays; single lab","pmids":["40115921"],"is_preprint":false},{"year":2021,"finding":"RPL14 overexpression in nasopharyngeal carcinoma (NPC) cells represses cell proliferation (blocking cells in S phase), migration, invasion, and the epithelial-mesenchymal transition (EMT) process, as evidenced by altered expression of E-cadherin, N-cadherin, and vimentin.","method":"CCK-8 assay; colony formation assay; cell cycle analysis; transwell migration/invasion assay; Western blot for EMT markers; overexpression via transfection","journal":"Bioengineered","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — gain-of-function with multiple cellular readouts; single lab, no rescue or epistasis experiments to place RPL14 in specific pathway","pmids":["34057029"],"is_preprint":false},{"year":2002,"finding":"Autoantibodies against ribosomal protein L14 are specifically detected in sera from patients with systemic lupus erythematosus (SLE) but not in patients with dermatomyositis/polymyositis, systemic sclerosis, or healthy controls, identified using GST-L14 fusion protein as antigen.","method":"Immunoblotting of total ribosomal proteins; 2D gel electrophoresis with immunoblotting for antigen identification; immunoblotting with recombinant GST-L14 fusion protein against 126 SLE and 212 control sera","journal":"Clinical and experimental rheumatology","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — antigen identification by 2D gel/immunoblot; specificity validated with recombinant protein; single lab, no mechanistic follow-up on why L14 is immunogenic in SLE","pmids":["12051391"],"is_preprint":false}],"current_model":"RPL14 (eL14) is an essential component of the eukaryotic 60S ribosomal large subunit that assembles early in the nucleolus into pre-60S particles; its depletion blocks 27SA pre-rRNA processing and pre-60S export, while its C-terminal eukaryote-specific extension influences translation fidelity. Structurally, L14 adopts a five-stranded beta-barrel with defined RNA- and protein-binding surfaces (including a likely interaction site with L19), and PRMT5-mediated symmetric dimethylation of RPL14 at arginine residues stabilizes the protein and promotes DNA damage repair, contributing to drug resistance in cancer cells."},"narrative":{"mechanistic_narrative":"RPL14 (eL14) is an essential structural protein of the eukaryotic 60S large ribosomal subunit, first isolated biochemically from rat liver ribosomes [PMID:621213] and later defined in human as a 220-amino-acid protein bearing nuclear targeting sequences, an rRNA-binding element, and a C-terminal polyalanine tract [PMID:9480843]. The protein adopts a five-stranded beta-barrel with discrete RNA- and protein-binding surface patches, including a hydrophobic patch implicated in contacting L19 [PMID:8805509], a functional L14–L19 interaction independently supported by compensatory-evolution genetics in which L14 mutations rescue the fitness costs of L19 mutations and influence translational decoding [PMID:17157877]. During ribosome biogenesis, L14 assembles early in the nucleolus into pre-60S particles; its depletion blocks processing of 27SA2/27SA3 to 27SB pre-rRNA, triggers turnover of 27S precursors, prevents pre-60S export, and reduces loading of neighboring ribosomal proteins at the solvent interface and polypeptide exit tunnel, while removal of its eukaryote-specific C-terminal extension alters translation fidelity [PMID:29788267]. Consistent with this essential role, RPL14 is dosage-sensitive: haploinsufficiency in Drosophila produces a Minute phenotype and RNAi knockdown below ~50% causes lethality and developmental anomalies [PMID:9236770, PMID:14597387]. Beyond ribosome assembly, PRMT5 binds RPL14 and catalyzes symmetric arginine dimethylation that stabilizes the protein, promotes DNA damage repair, and confers regorafenib resistance in hepatocellular carcinoma [PMID:40115921], and RPL14 overexpression suppresses proliferation, migration, invasion, and EMT in nasopharyngeal carcinoma cells [PMID:34057029].","teleology":[{"year":1978,"claim":"Established RPL14 as a bona fide protein constituent of the eukaryotic 60S large ribosomal subunit, providing the foundational identity for all downstream work.","evidence":"Ion-exchange and gel-filtration purification from native rat liver 60S subunits with SDS-PAGE and amino acid composition analysis","pmids":["621213"],"confidence":"High","gaps":["No structural or functional role assigned beyond subunit membership","No information on assembly stage or rRNA contacts"]},{"year":1978,"claim":"Showed that L14 is a target of metabolically regulated phosphorylation, raising the question of post-translational control of ribosomal proteins.","evidence":"Radiolabeled phosphorylation assays in Krebs II ascites cells under varying metabolic conditions","pmids":["27217"],"confidence":"Medium","gaps":["Responsible kinase and phosphosites not identified","Functional consequence of phosphorylation unknown"]},{"year":1989,"claim":"Defined how L14 synthesis is controlled in bacteria, showing translational/mRNA-stability retroregulation by S8 rather than autonomous regulation.","evidence":"Genetic site mutations, S8 overexpression in trans, and exonuclease-deficient strains in E. coli spc operon","pmids":["2643112"],"confidence":"High","gaps":["Bacterial operon regulation does not extend to eukaryotic RPL14","No direct test of S8–L14 mRNA contact in vivo structure"]},{"year":1994,"claim":"Identified a candidate transcription factor (FIII/YY1) binding the RPL14 promoter first exon, addressing how the gene might be transcriptionally controlled.","evidence":"cDNA cloning, oocyte overexpression, immunological characterization, and DNA-binding assays in Xenopus","pmids":["7802655"],"confidence":"Medium","gaps":["Binding alone did not establish a regulatory role","No demonstration of effect on transcription"]},{"year":1996,"claim":"Provided the atomic-level architecture of L14, defining the beta-barrel fold and mapping the surfaces that mediate rRNA contacts and a putative L19 interaction.","evidence":"X-ray crystallography (isomorphous replacement/MAD) of L14 from Bacillus stearothermophilus with surface patch analysis","pmids":["8805509"],"confidence":"High","gaps":["Bacterial structure lacks the eukaryote-specific C-terminal extension","L19 interaction proposed from surface analysis, not directly co-crystallized"]},{"year":1996,"claim":"Characterized the human RPL14 transcript and protein, defining domains including nuclear targeting sequences, an rRNA-binding element, and a polyalanine tract.","evidence":"cDNA cloning/sequencing from a human endothelial library with Northern blot and bioinformatic domain analysis","pmids":["9480843"],"confidence":"Medium","gaps":["No functional assays of the predicted domains","Role of the polyalanine tract unknown"]},{"year":1997,"claim":"Demonstrated that RPL14 is haploinsufficient and dosage-sensitive in a metazoan, linking reduced gene dosage to a defined developmental Minute phenotype.","evidence":"Drosophila P-element insertion with quantitative Northern blot and P-element remobilization rescue","pmids":["9236770"],"confidence":"High","gaps":["Molecular basis of the Minute phenotype at the ribosome level not resolved","No human disease link established here"]},{"year":1998,"claim":"Resolved the FIII/YY1 question with a negative result, showing the binding sites are dispensable for RPL14 promoter activity.","evidence":"CAT reporter assays with mutated FIII/YY1 sites in Xenopus oocytes and kidney cells plus FIII/YY1 overexpression","pmids":["9738894"],"confidence":"Medium","gaps":["Actual cis-elements driving RPL14 transcription not identified","Limited to Xenopus reporter systems"]},{"year":2002,"claim":"Identified RPL14 as an SLE-specific autoantigen, raising the question of why a ribosomal protein becomes immunogenic in autoimmunity.","evidence":"2D gel/immunoblot antigen identification and recombinant GST-L14 immunoblotting against 126 SLE and 212 control sera","pmids":["12051391"],"confidence":"Medium","gaps":["Mechanism of immunogenicity unexplored","No causal link between autoantibody and disease pathology"]},{"year":2003,"claim":"Confirmed that RPL14 is essential for viability and proliferation when reduced below ~50%, reinforcing its dosage-critical role across tissues.","evidence":"Spatiotemporal GAL4/UAS RNAi knockdown in Drosophila with RNA-level verification and phenotypic analysis","pmids":["14597387"],"confidence":"High","gaps":["Did not distinguish ribosome-assembly defects from extra-ribosomal effects","No molecular pathway dissection"]},{"year":2006,"claim":"Provided functional genetic evidence for the L14–L19 interaction predicted structurally, linking it to translational decoding accuracy.","evidence":"Compensatory-evolution serial passage in Salmonella with fitness, UGA read-through, and aminoglycoside sensitivity assays","pmids":["17157877"],"confidence":"High","gaps":["Bacterial context; eukaryotic L14–L19 contact not directly tested here","Mechanism of decoding modulation not resolved at atomic level"]},{"year":2018,"claim":"Placed eL14 in the ribosome biogenesis pathway, showing it acts early in nucleolar pre-60S assembly to drive 27S pre-rRNA processing, pre-60S export, and neighbor-protein loading, with the C-terminal extension tuning translation fidelity.","evidence":"Conditional depletion in S. cerevisiae with Northern blot of pre-rRNA intermediates, sucrose gradient sedimentation, factor co-sedimentation, and C-terminal truncation mutants","pmids":["29788267"],"confidence":"High","gaps":["Direct structural snapshot of eL14 within human pre-60S not provided","Precise mechanism by which the C-terminal extension affects fidelity unresolved"]},{"year":2021,"claim":"Linked RPL14 levels to cancer cell behavior, showing overexpression suppresses proliferation, migration, invasion, and EMT in nasopharyngeal carcinoma.","evidence":"Gain-of-function transfection with CCK-8, colony formation, cell cycle, transwell, and EMT-marker Western blots","pmids":["34057029"],"confidence":"Medium","gaps":["No rescue or epistasis to place RPL14 in a defined pathway","Single tumor type; mechanism of EMT suppression unknown"]},{"year":2025,"claim":"Revealed an extra-ribosomal regulatory axis: PRMT5-catalyzed symmetric arginine dimethylation stabilizes RPL14 and couples it to DNA damage repair and chemoresistance.","evidence":"Mass spectrometry, co-immunoprecipitation, siRNA knockdown, PRMT5 overexpression, and γ-H2AX/RAD51 Western blot/immunofluorescence in hepatocellular carcinoma cells","pmids":["40115921"],"confidence":"Medium","gaps":["Specific methylated arginine residues not mapped","Mechanistic link between RPL14 and RAD51-mediated repair undefined","Single lab and single tumor model"]},{"year":null,"claim":"How RPL14's structural role in 60S assembly mechanistically connects to its extra-ribosomal functions in DNA damage repair, EMT regulation, and chemoresistance remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of human eL14 within the assembled ribosome or pre-60S","Unknown whether cancer phenotypes arise from altered translation or moonlighting activity","PRMT5-dependent and ribosome-assembly functions not integrated in a single model"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,5]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0,5,10]}],"localization":[{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[1,5]},{"term_id":"GO:0005730","term_label":"nucleolus","supporting_discovery_ids":[5]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[5]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[1,5]}],"complexes":["60S large ribosomal subunit","pre-60S particle"],"partners":["RPL19","PRMT5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P50914","full_name":"Large ribosomal subunit protein eL14","aliases":["60S ribosomal protein L14","CAG-ISL 7"],"length_aa":215,"mass_kda":23.4,"function":"Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:32669547)","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/P50914/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/RPL14","classification":"Common Essential","n_dependent_lines":1208,"n_total_lines":1208,"dependency_fraction":1.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"RPL11","stoichiometry":10.0},{"gene":"RPL4","stoichiometry":10.0},{"gene":"EIF2S3","stoichiometry":4.0},{"gene":"EIF3G","stoichiometry":4.0},{"gene":"RACK1","stoichiometry":4.0},{"gene":"RBM8A","stoichiometry":4.0},{"gene":"RPL13","stoichiometry":4.0},{"gene":"RPL5","stoichiometry":4.0},{"gene":"RPS16","stoichiometry":4.0},{"gene":"SRP68","stoichiometry":4.0}],"url":"https://opencell.sf.czbiohub.org/search/RPL14","total_profiled":1310},"omim":[{"mim_id":"617414","title":"RIBOSOMAL PROTEIN L14; RPL14","url":"https://www.omim.org/entry/617414"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Endoplasmic reticulum","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/RPL14"},"hgnc":{"alias_symbol":["L14","hRL14","RL14","CTG-B33","eL14"],"prev_symbol":[]},"alphafold":{"accession":"P50914","domains":[{"cath_id":"2.30.30.30","chopping":"12-102","consensus_level":"high","plddt":96.1781,"start":12,"end":102},{"cath_id":"1.20.5","chopping":"105-139","consensus_level":"high","plddt":95.1297,"start":105,"end":139}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P50914","model_url":"https://alphafold.ebi.ac.uk/files/AF-P50914-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P50914-F1-predicted_aligned_error_v6.png","plddt_mean":76.56},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=RPL14","jax_strain_url":"https://www.jax.org/strain/search?query=RPL14"},"sequence":{"accession":"P50914","fasta_url":"https://rest.uniprot.org/uniprotkb/P50914.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P50914/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P50914"}},"corpus_meta":[{"pmid":"8306885","id":"PMC_8306885","title":"Normal development of mice carrying a null mutation in the gene encoding the L14 S-type lectin.","date":"1993","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/8306885","citation_count":197,"is_preprint":false},{"pmid":"8175907","id":"PMC_8175907","title":"Selective modulation of the interaction of alpha 7 beta 1 integrin with fibronectin and laminin by L-14 lectin during skeletal muscle differentiation.","date":"1994","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/8175907","citation_count":153,"is_preprint":false},{"pmid":"1638977","id":"PMC_1638977","title":"Expression of the L14 lectin during mouse embryogenesis suggests multiple roles during pre- and post-implantation development.","date":"1992","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/1638977","citation_count":137,"is_preprint":false},{"pmid":"8050350","id":"PMC_8050350","title":"Rat olfactory neurons can utilize the endogenous lectin, L-14, in a novel adhesion mechanism.","date":"1994","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/8050350","citation_count":137,"is_preprint":false},{"pmid":"621213","id":"PMC_621213","title":"Isolation of eukaryotic ribosomal proteins. Purification and characterization of the 60 S ribosomal subunit proteins La, Lb, Lf, P1, P2, L13', L14, L18', L20, and L38.","date":"1978","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/621213","citation_count":112,"is_preprint":false},{"pmid":"8380972","id":"PMC_8380972","title":"L-14 lectin recognition of laminin and its promotion of in vitro cell adhesion.","date":"1993","source":"Archives of biochemistry and biophysics","url":"https://pubmed.ncbi.nlm.nih.gov/8380972","citation_count":104,"is_preprint":false},{"pmid":"33291425","id":"PMC_33291425","title":"Exopolysaccharide Isolated from Lactobacillus plantarum L-14 Has Anti-Inflammatory Effects via the Toll-Like Receptor 4 Pathway in LPS-Induced RAW 264.7 Cells.","date":"2020","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/33291425","citation_count":65,"is_preprint":false},{"pmid":"8805509","id":"PMC_8805509","title":"The crystal structure of ribosomal protein L14 reveals an important organizational component of the translational apparatus.","date":"1996","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/8805509","citation_count":59,"is_preprint":false},{"pmid":"2643112","id":"PMC_2643112","title":"Retroregulation of the synthesis of ribosomal proteins L14 and L24 by feedback repressor S8 in Escherichia coli.","date":"1989","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/2643112","citation_count":52,"is_preprint":false},{"pmid":"33830560","id":"PMC_33830560","title":"Oral intake of Lactobacillus plantarum L-14 extract alleviates TLR2- and AMPK-mediated obesity-associated disorders in high-fat-diet-induced obese C57BL/6J mice.","date":"2021","source":"Cell proliferation","url":"https://pubmed.ncbi.nlm.nih.gov/33830560","citation_count":51,"is_preprint":false},{"pmid":"4018095","id":"PMC_4018095","title":"The complete primary structure of ribosomal proteins L1, L14, L15, L23, L24 and L29 from Bacillus stearothermophilus.","date":"1985","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/4018095","citation_count":50,"is_preprint":false},{"pmid":"17157877","id":"PMC_17157877","title":"Compensatory evolution reveals functional interactions between ribosomal proteins S12, L14 and L19.","date":"2006","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17157877","citation_count":49,"is_preprint":false},{"pmid":"7802655","id":"PMC_7802655","title":"Characterization of FIII/YY1, a Xenopus laevis conserved zinc-finger protein binding to the first exon of L1 and L14 ribosomal protein genes.","date":"1994","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/7802655","citation_count":38,"is_preprint":false},{"pmid":"25600587","id":"PMC_25600587","title":"5-, 12- and 15-Hydroxyeicosatetraenoic acids induce cellular hypertrophy in the human ventricular cardiomyocyte, RL-14 cell line, through MAPK- and NF-κB-dependent mechanism.","date":"2015","source":"Archives of toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/25600587","citation_count":37,"is_preprint":false},{"pmid":"3774540","id":"PMC_3774540","title":"Sequences coding for the ribosomal protein L14 in Xenopus laevis and Xenopus tropicalis; homologies in the 5' untranslated region are shared with other r-protein mRNAs.","date":"1986","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/3774540","citation_count":36,"is_preprint":false},{"pmid":"26493311","id":"PMC_26493311","title":"Development of cellular hypertrophy by 8-hydroxyeicosatetraenoic acid in the human ventricular cardiomyocyte, RL-14 cell line, is implicated by MAPK and NF-κB.","date":"2015","source":"Cell biology and toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/26493311","citation_count":33,"is_preprint":false},{"pmid":"9920051","id":"PMC_9920051","title":"Trinucleotide repeat length variation in the human ribosomal protein L14 gene (RPL14): localization to 3p21.3 and loss of heterozygosity in lung and oral cancers.","date":"1998","source":"Mutation research","url":"https://pubmed.ncbi.nlm.nih.gov/9920051","citation_count":28,"is_preprint":false},{"pmid":"9236770","id":"PMC_9236770","title":"The Drosophila ribosomal protein L14-encoding gene, identified by a novel Minute mutation in a dense cluster of previously undescribed genes in cytogenetic region 66D.","date":"1997","source":"Molecular & general genetics : MGG","url":"https://pubmed.ncbi.nlm.nih.gov/9236770","citation_count":28,"is_preprint":false},{"pmid":"16316724","id":"PMC_16316724","title":"Alteration of RPL14 in squamous cell carcinomas and preneoplastic lesions of the esophagus.","date":"2005","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/16316724","citation_count":25,"is_preprint":false},{"pmid":"25454080","id":"PMC_25454080","title":"Human fetal ventricular cardiomyocyte, RL-14 cell line, is a promising model to study drug metabolizing enzymes and their associated arachidonic acid metabolites.","date":"2014","source":"Journal of pharmacological and toxicological methods","url":"https://pubmed.ncbi.nlm.nih.gov/25454080","citation_count":25,"is_preprint":false},{"pmid":"8609496","id":"PMC_8609496","title":"Cell-mediated immunity to pseudorabies virus: cytolytic effector cells with characteristics of lymphokine-activated killer cells lyse virus-infected and glycoprotein gB- and gC-transfected L14 cells.","date":"1996","source":"The Journal of general virology","url":"https://pubmed.ncbi.nlm.nih.gov/8609496","citation_count":25,"is_preprint":false},{"pmid":"2137906","id":"PMC_2137906","title":"Analysis of NADH dehydrogenase proteins, ATPase subunit 9, cytochrome b, and ribosomal protein L14 encoded in the mitochondrial DNA of Paramecium.","date":"1990","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/2137906","citation_count":24,"is_preprint":false},{"pmid":"27217","id":"PMC_27217","title":"The phosphorylation of ribosomal proteins L14 and S3 in Krebs II ascites cells.","date":"1978","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/27217","citation_count":24,"is_preprint":false},{"pmid":"15877432","id":"PMC_15877432","title":"Effect of 2-(2-Pyridyl)azole-based ancillary ligands (L1-4) on the electrophilicity of the nitrosyl function in [RuII(trpy)(L1-)4)(NO)]3+ [trpy = 2,2':6',2' '-Terpyridine]. synthesis, structures, and spectroscopic, electrochemical, and kinetic aspects.","date":"2005","source":"Inorganic chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15877432","citation_count":23,"is_preprint":false},{"pmid":"7578105","id":"PMC_7578105","title":"The single-ring Thermoanaerobacter brockii chaperonin 60 (Tbr-EL7) dimerizes to Tbr-EL14.Tbr-ES7 under protein folding conditions.","date":"1995","source":"Biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/7578105","citation_count":22,"is_preprint":false},{"pmid":"33505161","id":"PMC_33505161","title":"Propofol Inhibits the Progression of Cervical Cancer by Regulating HOTAIR/miR-129-5p/RPL14 Axis.","date":"2021","source":"OncoTargets and therapy","url":"https://pubmed.ncbi.nlm.nih.gov/33505161","citation_count":21,"is_preprint":false},{"pmid":"32859054","id":"PMC_32859054","title":"Anti-Cancer Effects of Lactobacillus plantarum L-14 Cell-Free Extract on Human Malignant Melanoma A375 Cells.","date":"2020","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/32859054","citation_count":21,"is_preprint":false},{"pmid":"14597387","id":"PMC_14597387","title":"Silencing the Drosophila ribosomal protein L14 gene using targeted RNA interference causes distinct somatic anomalies.","date":"2003","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/14597387","citation_count":19,"is_preprint":false},{"pmid":"37627510","id":"PMC_37627510","title":"Ameliorative Effects of Lactobacillus paracasei L14 on Oxidative Stress and Gut Microbiota in Type 2 Diabetes Mellitus Rats.","date":"2023","source":"Antioxidants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/37627510","citation_count":18,"is_preprint":false},{"pmid":"8135794","id":"PMC_8135794","title":"Expression of the soluble lectin L-14 gene is induced by TSH in thyroid cells and suppressed by retinoic acid in transformed neural cells.","date":"1994","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/8135794","citation_count":15,"is_preprint":false},{"pmid":"9480843","id":"PMC_9480843","title":"Triplet repeat-containing ribosomal protein L14 gene in immortalized human endothelial cell line (t-HUE4).","date":"1998","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/9480843","citation_count":14,"is_preprint":false},{"pmid":"27764251","id":"PMC_27764251","title":"Heterologous Expression and Delivery of Biologically Active Exendin-4 by Lactobacillus paracasei L14.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27764251","citation_count":14,"is_preprint":false},{"pmid":"8670222","id":"PMC_8670222","title":"The primary structure of rat ribosomal protein L14.","date":"1996","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/8670222","citation_count":14,"is_preprint":false},{"pmid":"15040916","id":"PMC_15040916","title":"Discrimination among species of Papaver based on the plastid rpl16 gene and the rpl16-rpl14 spacer sequence.","date":"2004","source":"Forensic science international","url":"https://pubmed.ncbi.nlm.nih.gov/15040916","citation_count":13,"is_preprint":false},{"pmid":"2163974","id":"PMC_2163974","title":"DXS28 (C7) maps centromeric to DXS68 (L1-4) and DXS67 (B24) by deletion analysis.","date":"1990","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/2163974","citation_count":13,"is_preprint":false},{"pmid":"34057029","id":"PMC_34057029","title":"Human/eukaryotic ribosomal protein L14 (RPL14/eL14) overexpression represses proliferation, migration, invasion and EMT process in nasopharyngeal carcinoma.","date":"2021","source":"Bioengineered","url":"https://pubmed.ncbi.nlm.nih.gov/34057029","citation_count":12,"is_preprint":false},{"pmid":"36822197","id":"PMC_36822197","title":"Mitochondrial Ribosomal Protein L14 Promotes Cell Growth and Invasion by Modulating Reactive Oxygen Species in Thyroid Cancer.","date":"2023","source":"Clinical and experimental otorhinolaryngology","url":"https://pubmed.ncbi.nlm.nih.gov/36822197","citation_count":12,"is_preprint":false},{"pmid":"35736074","id":"PMC_35736074","title":"Genomic and AntiSMASH Analyses of Marine-Sponge-Derived Strain Aspergillus niger L14 Unveiling Its Vast Potential of Secondary Metabolites Biosynthesis.","date":"2022","source":"Journal of fungi (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/35736074","citation_count":12,"is_preprint":false},{"pmid":"29788267","id":"PMC_29788267","title":"Ribosomal protein L14 contributes to the early assembly of 60S ribosomal subunits in Saccharomyces cerevisiae.","date":"2018","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/29788267","citation_count":11,"is_preprint":false},{"pmid":"11853170","id":"PMC_11853170","title":"Pharmacognostical studies of cistanchis herba (III) phylogenetic relationship of the cistanche plants based on plastid rps2 gene and rpl16-rpl14 intergenic spacer sequences.","date":"2002","source":"Biological & pharmaceutical bulletin","url":"https://pubmed.ncbi.nlm.nih.gov/11853170","citation_count":10,"is_preprint":false},{"pmid":"15588583","id":"PMC_15588583","title":"Preferential expression of a HLP homolog encoding a mitochondrial L14 ribosomal protein in stamens of common wheat.","date":"2004","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/15588583","citation_count":9,"is_preprint":false},{"pmid":"7949655","id":"PMC_7949655","title":"Xenopus laevis L-14 lectin is expressed in a typical pattern in the adult, but is absent from embryonic tissues.","date":"1994","source":"Glycobiology","url":"https://pubmed.ncbi.nlm.nih.gov/7949655","citation_count":9,"is_preprint":false},{"pmid":"40536697","id":"PMC_40536697","title":"Ezetimibe Engineered L14-8 Suppresses Advanced Prostate Cancer by Activating PLK1/TP53-SAT1-Induced Ferroptosis.","date":"2025","source":"Advanced science (Weinheim, Baden-Wurttemberg, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/40536697","citation_count":7,"is_preprint":false},{"pmid":"15848027","id":"PMC_15848027","title":"The sequences of the plastid gene rpl16 and the rpl16-rpl14 spacer region allow discrimination among six species of Scutellaria.","date":"2005","source":"Journal of ethnopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/15848027","citation_count":7,"is_preprint":false},{"pmid":"9738894","id":"PMC_9738894","title":"The binding sites for Xenopus laevis FIII/YY1 in the first exon of L1 and L14 ribosomal protein genes are dispensable for promoter expression.","date":"1998","source":"European journal of biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9738894","citation_count":6,"is_preprint":false},{"pmid":"12051391","id":"PMC_12051391","title":"Autoantibody against ribosomal protein L14 in patients with systemic lupus erythematosus.","date":"2002","source":"Clinical and experimental rheumatology","url":"https://pubmed.ncbi.nlm.nih.gov/12051391","citation_count":6,"is_preprint":false},{"pmid":"32092082","id":"PMC_32092082","title":"Development of endomyocardial fibrosis model using a cell patterning technique: In vitro interaction of cell coculture of 3T3 fibroblasts and RL-14 cardiomyocytes.","date":"2020","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/32092082","citation_count":6,"is_preprint":false},{"pmid":"37815672","id":"PMC_37815672","title":"The Effects of 16-HETE Enantiomers on Hypertrophic Markers in Human Fetal Ventricular Cardiomyocytes, RL-14 Cells.","date":"2023","source":"European journal of drug metabolism and pharmacokinetics","url":"https://pubmed.ncbi.nlm.nih.gov/37815672","citation_count":5,"is_preprint":false},{"pmid":"15299380","id":"PMC_15299380","title":"Crystallization and preliminary X-ray diffraction studies of bacterial ribosomal protein L14.","date":"1994","source":"Acta crystallographica. Section D, Biological crystallography","url":"https://pubmed.ncbi.nlm.nih.gov/15299380","citation_count":5,"is_preprint":false},{"pmid":"15030001","id":"PMC_15030001","title":"Molecular and immunological characterization of L14 ribosomal protein from Leishmania braziliensis.","date":"2004","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15030001","citation_count":4,"is_preprint":false},{"pmid":"35582492","id":"PMC_35582492","title":"In Vitro and in Vivo Activity of Lactobacillus Sakei L14 Strain Against Campylobacter Jejuni DC3 Strain.","date":"2022","source":"Journal of veterinary research","url":"https://pubmed.ncbi.nlm.nih.gov/35582492","citation_count":3,"is_preprint":false},{"pmid":"15061815","id":"PMC_15061815","title":"Identification and comparative analysis of the RpL14 gene from Takifugu rubripes.","date":"2003","source":"Hereditas","url":"https://pubmed.ncbi.nlm.nih.gov/15061815","citation_count":2,"is_preprint":false},{"pmid":"40115921","id":"PMC_40115921","title":"PRMT5 attenuates regorafenib-induced DNA damage in hepatocellular carcinoma cells through symmetric dimethylation of RPL14.","date":"2025","source":"Journal of gastrointestinal oncology","url":"https://pubmed.ncbi.nlm.nih.gov/40115921","citation_count":2,"is_preprint":false},{"pmid":"9522130","id":"PMC_9522130","title":"Primary structure of Drosophila ribosomal protein L14 and identification of conserved protein motifs.","date":"1997","source":"DNA sequence : the journal of DNA sequencing and mapping","url":"https://pubmed.ncbi.nlm.nih.gov/9522130","citation_count":2,"is_preprint":false},{"pmid":"39663999","id":"PMC_39663999","title":"Overexpression of the Global Transcriptional Regulator LaeA Leads to Production of Cyclic Lipopeptides in Marine-Derived Aspergillus niger L14.","date":"2024","source":"Chemistry & biodiversity","url":"https://pubmed.ncbi.nlm.nih.gov/39663999","citation_count":2,"is_preprint":false},{"pmid":"16934181","id":"PMC_16934181","title":"A novel full-length gene of human ribosomal protein L14.22 related to human glioma.","date":"2006","source":"Chinese medical journal","url":"https://pubmed.ncbi.nlm.nih.gov/16934181","citation_count":0,"is_preprint":false},{"pmid":"32336715","id":"PMC_32336715","title":"[Identification of Plant Fragments by Analyzing the Plastid rpl16-rpl14 Linker Sequences].","date":"2020","source":"Shokuhin eiseigaku zasshi. Journal of the Food Hygienic Society of Japan","url":"https://pubmed.ncbi.nlm.nih.gov/32336715","citation_count":0,"is_preprint":false},{"pmid":"42187809","id":"PMC_42187809","title":"From Contact to Stalemate: MAPK-Associated Chemical and Enzymatic Defenses Shape a Stable Barrage in the Co-Culture of Trametes sp. D and Aspergillus niger L14.","date":"2026","source":"Journal of fungi (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/42187809","citation_count":0,"is_preprint":false},{"pmid":"41879162","id":"PMC_41879162","title":"Heat-Treated Culture-Dried Lactiplantibacillus plantarum L-14 Regulates Lipid Metabolism and Attenuates Diet-Induced Obesity in Adipose Tissue.","date":"2026","source":"Journal of medicinal food","url":"https://pubmed.ncbi.nlm.nih.gov/41879162","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.09.16.675553","title":"Kinetic mechanism of Renilla luciferase guides induced-fit engineering for improved bioluminescence","date":"2025-09-18","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.16.675553","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":29816,"output_tokens":3705,"usd":0.072512,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11398,"output_tokens":4207,"usd":0.081083,"stage2_stop_reason":"end_turn"},"total_usd":0.153595,"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\": 1996,\n      \"finding\": \"Crystal structure of ribosomal protein L14 from Bacillus stearothermophilus was solved, revealing a five-stranded beta-barrel, a C-terminal loop region with two small alpha-helices, and a beta-ribbon projecting from the barrel. Analysis identified three surface patches likely mediating L14-RNA and L14-protein interactions, with two RNA-binding sites and a hydrophobic patch proposed as an L19 protein-protein interaction site.\",\n      \"method\": \"X-ray crystallography using isomorphous replacement and MAD methods, solved to high resolution\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure with functional surface analysis; single study but high-resolution structural determination with mutagenesis-guided interpretation\",\n      \"pmids\": [\"8805509\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1978,\n      \"finding\": \"Ribosomal protein L14 was purified from the 60S large ribosomal subunit of rat liver ribosomes, establishing it as a component of the eukaryotic 60S subunit with a defined molecular weight estimated by SDS-PAGE.\",\n      \"method\": \"Protein purification via ion-exchange chromatography (carboxymethylcellulose, DEAE-cellulose) and gel filtration; molecular weight by SDS-PAGE; amino acid composition analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct biochemical isolation and characterization of the protein from native ribosomal subunits; foundational biochemistry paper\",\n      \"pmids\": [\"621213\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1978,\n      \"finding\": \"Ribosomal protein L14 in Krebs II ascites cells becomes phosphorylated when cells are incubated in Eagle's medium (glucose + amino acids), a condition that also causes dephosphorylation of Lgamma, suggesting that metabolic state regulates the pattern of ribosomal protein phosphorylation.\",\n      \"method\": \"Radiolabeled phosphorylation assays in Krebs II ascites cells under varying metabolic conditions; comparison of phosphorylation patterns on ribosomal proteins\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct phosphorylation detection in intact cells, single study, metabolic manipulation shows context-dependent modification\",\n      \"pmids\": [\"27217\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1989,\n      \"finding\": \"In E. coli, ribosomal protein S8 retroregulates synthesis of L14 and L24 (the first and second gene products of the spc operon) by acting at an mRNA target site distal to the L14/L24 coding sequences; mRNA degradation by 3'-to-5' exonucleases (polynucleotide phosphorylase and RNase II) is the mechanism of this retroregulation.\",\n      \"method\": \"Genetic analysis using single-base substitutions in the S8 target site; S8 overexpression in trans from a plasmid; temperature-sensitive mutations in polynucleotide phosphorylase and RNase II genes; differential synthesis rate measurements\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple genetic approaches (site mutations, overexpression, exonuclease-deficient strains) in a single rigorous study establishing retroregulation mechanism\",\n      \"pmids\": [\"2643112\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Compensatory evolution experiments in Salmonella typhimurium revealed that mutations in L14 can compensate for fitness costs of L19 mutations, demonstrating a functional interaction between L14 and L19 in the 50S subunit. L14 is located close to L19, and their interaction with 16S rRNA may influence 30S subunit function during the decoding step of translation.\",\n      \"method\": \"In vivo fitness measurements, serial passage for compensatory evolution, translation speed and accuracy assays (UGA read-through), aminoglycoside sensitivity testing, genetic epistasis\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal in vivo methods (fitness, accuracy, drug sensitivity) demonstrating functional L14-L19 interaction; replicated across multiple mutant backgrounds\",\n      \"pmids\": [\"17157877\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"In Saccharomyces cerevisiae, L14 (eL14) assembles in the nucleolus at an early stage into pre-60S particles. Depletion of L14 causes defective processing of 27SA2 and 27SA3 to 27SB pre-rRNAs, leads to turnover of 27S pre-rRNAs, blocks export of pre-60S particles, and reduces association of neighboring ribosomal proteins at the solvent interface and around the polypeptide exit tunnel. Removal of the distal eukaryote-specific C-terminal extensions of L14 and L16 causes slight translation alterations in mature 60S subunits.\",\n      \"method\": \"Conditional depletion of L14; Northern blot analysis of pre-rRNA processing intermediates; sucrose gradient sedimentation; co-sedimentation of trans-acting factors; C-terminal truncation mutants analyzed for translation fidelity\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional depletion with multiple orthogonal readouts (pre-rRNA processing, export, factor association, translation); rigorous yeast ribosome biogenesis study\",\n      \"pmids\": [\"29788267\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"Haploinsufficiency of the Drosophila RPL14 gene (caused by a P-element insertion in the RPL14 promoter region) causes a strong Minute phenotype (short thin bristles, developmental delay, recessive lethality), establishing RPL14 as a dosage-sensitive ribosomal protein gene. Quantitative Northern blot showed reduction in RPL14 mRNA; remobilization of the P element restored wild-type RPL14 mRNA levels and normal phenotype.\",\n      \"method\": \"P-element mutagenesis; quantitative Northern blot; P-element remobilization rescue experiment; phenotypic analysis\",\n      \"journal\": \"Molecular & general genetics : MGG\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function with molecular confirmation and rescue experiment demonstrating causality\",\n      \"pmids\": [\"9236770\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Targeted RNA interference (RNAi) knockdown of Drosophila RpL14 using the GAL4/UAS system causes lethality and distinct somatic anomalies in both developing and differentiated cells, demonstrating that RPL14 is essential for normal cell proliferation and development when reduced below 50% of normal levels.\",\n      \"method\": \"Heritable RNAi via GAL4/UAS binary system; RNA-level confirmation of knockdown; phenotypic analysis of developing and differentiated tissues\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — spatiotemporal RNAi knockdown with RNA-level verification and defined phenotypic readouts; single lab but multiple tissue contexts examined\",\n      \"pmids\": [\"14597387\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1994,\n      \"finding\": \"The transcription factor FIII/YY1 (Xenopus homolog of human YY1/delta) binds to the first exon of the Xenopus laevis ribosomal protein L14 gene. The protein was identified to share antigenic and DNA-binding properties with the endogenous oocyte protein that contacts the first exon of rp genes L1 and L14.\",\n      \"method\": \"cDNA cloning; overexpression in Xenopus oocytes; immunological characterization; DNA-binding assays\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct binding demonstrated by DNA-binding assay and immunological cross-reactivity; single lab, single study\",\n      \"pmids\": [\"7802655\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"FIII/YY1 binding sites in the first exon of Xenopus laevis RPL14 (and L1) promoters are dispensable for promoter expression: mutations in the FIII/YY1 sites did not change reporter (CAT) activity in oocyte injection assays or in transfected Xenopus kidney cells, and overexpression of FIII/YY1 had no effect.\",\n      \"method\": \"CAT reporter assays with wild-type and mutated FIII/YY1 binding sites; oocyte microinjection; cell transfection; FIII/YY1 overexpression\",\n      \"journal\": \"European journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — negative functional result established by two orthogonal cell systems (oocytes and kidney cells); single lab\",\n      \"pmids\": [\"9738894\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"Human RPL14 (hRL14) encodes a 60S ribosomal subunit protein of 220 amino acids (predicted MW 23.6 kDa) containing nuclear targeting sequences, a bZIP-like element for rRNA binding, and internal pentapeptide repeat sequences. The COOH-terminal region contains 15 GCT (alanine) triplet repeats encoding a polyalanine tract.\",\n      \"method\": \"cDNA cloning and sequencing from human endothelial cell library; Northern blot analysis; bioinformatic domain analysis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — primary structural characterization of the human protein with functional domain identification; no direct functional assays performed\",\n      \"pmids\": [\"9480843\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PRMT5 interacts with RPL14 and catalyzes symmetric dimethylation of RPL14 at arginine residues. This modification stabilizes RPL14 protein, promotes DNA damage repair (as measured by RAD51 expression), and contributes to regorafenib resistance in hepatocellular carcinoma cells. RPL14 knockdown increases DNA damage (γ-H2AX), reduces cell viability, and increases sensitivity to regorafenib.\",\n      \"method\": \"Mass spectrometry; co-immunoprecipitation; Western blot for γ-H2AX and RAD51; lentiviral PRMT5 overexpression; siRNA knockdown; immunofluorescence\",\n      \"journal\": \"Journal of gastrointestinal oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — interaction confirmed by mass spectrometry and Co-IP; functional consequence of dimethylation shown by multiple assays; single lab\",\n      \"pmids\": [\"40115921\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"RPL14 overexpression in nasopharyngeal carcinoma (NPC) cells represses cell proliferation (blocking cells in S phase), migration, invasion, and the epithelial-mesenchymal transition (EMT) process, as evidenced by altered expression of E-cadherin, N-cadherin, and vimentin.\",\n      \"method\": \"CCK-8 assay; colony formation assay; cell cycle analysis; transwell migration/invasion assay; Western blot for EMT markers; overexpression via transfection\",\n      \"journal\": \"Bioengineered\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — gain-of-function with multiple cellular readouts; single lab, no rescue or epistasis experiments to place RPL14 in specific pathway\",\n      \"pmids\": [\"34057029\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Autoantibodies against ribosomal protein L14 are specifically detected in sera from patients with systemic lupus erythematosus (SLE) but not in patients with dermatomyositis/polymyositis, systemic sclerosis, or healthy controls, identified using GST-L14 fusion protein as antigen.\",\n      \"method\": \"Immunoblotting of total ribosomal proteins; 2D gel electrophoresis with immunoblotting for antigen identification; immunoblotting with recombinant GST-L14 fusion protein against 126 SLE and 212 control sera\",\n      \"journal\": \"Clinical and experimental rheumatology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — antigen identification by 2D gel/immunoblot; specificity validated with recombinant protein; single lab, no mechanistic follow-up on why L14 is immunogenic in SLE\",\n      \"pmids\": [\"12051391\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"RPL14 (eL14) is an essential component of the eukaryotic 60S ribosomal large subunit that assembles early in the nucleolus into pre-60S particles; its depletion blocks 27SA pre-rRNA processing and pre-60S export, while its C-terminal eukaryote-specific extension influences translation fidelity. Structurally, L14 adopts a five-stranded beta-barrel with defined RNA- and protein-binding surfaces (including a likely interaction site with L19), and PRMT5-mediated symmetric dimethylation of RPL14 at arginine residues stabilizes the protein and promotes DNA damage repair, contributing to drug resistance in cancer cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPL14 (eL14) is an essential structural protein of the eukaryotic 60S large ribosomal subunit, first isolated biochemically from rat liver ribosomes [#1] and later defined in human as a 220-amino-acid protein bearing nuclear targeting sequences, an rRNA-binding element, and a C-terminal polyalanine tract [#10]. The protein adopts a five-stranded beta-barrel with discrete RNA- and protein-binding surface patches, including a hydrophobic patch implicated in contacting L19 [#0], a functional L14–L19 interaction independently supported by compensatory-evolution genetics in which L14 mutations rescue the fitness costs of L19 mutations and influence translational decoding [#4]. During ribosome biogenesis, L14 assembles early in the nucleolus into pre-60S particles; its depletion blocks processing of 27SA2/27SA3 to 27SB pre-rRNA, triggers turnover of 27S precursors, prevents pre-60S export, and reduces loading of neighboring ribosomal proteins at the solvent interface and polypeptide exit tunnel, while removal of its eukaryote-specific C-terminal extension alters translation fidelity [#5]. Consistent with this essential role, RPL14 is dosage-sensitive: haploinsufficiency in Drosophila produces a Minute phenotype and RNAi knockdown below ~50% causes lethality and developmental anomalies [#6, #7]. Beyond ribosome assembly, PRMT5 binds RPL14 and catalyzes symmetric arginine dimethylation that stabilizes the protein, promotes DNA damage repair, and confers regorafenib resistance in hepatocellular carcinoma [#11], and RPL14 overexpression suppresses proliferation, migration, invasion, and EMT in nasopharyngeal carcinoma cells [#12].\",\n  \"teleology\": [\n    {\n      \"year\": 1978,\n      \"claim\": \"Established RPL14 as a bona fide protein constituent of the eukaryotic 60S large ribosomal subunit, providing the foundational identity for all downstream work.\",\n      \"evidence\": \"Ion-exchange and gel-filtration purification from native rat liver 60S subunits with SDS-PAGE and amino acid composition analysis\",\n      \"pmids\": [\"621213\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural or functional role assigned beyond subunit membership\", \"No information on assembly stage or rRNA contacts\"]\n    },\n    {\n      \"year\": 1978,\n      \"claim\": \"Showed that L14 is a target of metabolically regulated phosphorylation, raising the question of post-translational control of ribosomal proteins.\",\n      \"evidence\": \"Radiolabeled phosphorylation assays in Krebs II ascites cells under varying metabolic conditions\",\n      \"pmids\": [\"27217\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Responsible kinase and phosphosites not identified\", \"Functional consequence of phosphorylation unknown\"]\n    },\n    {\n      \"year\": 1989,\n      \"claim\": \"Defined how L14 synthesis is controlled in bacteria, showing translational/mRNA-stability retroregulation by S8 rather than autonomous regulation.\",\n      \"evidence\": \"Genetic site mutations, S8 overexpression in trans, and exonuclease-deficient strains in E. coli spc operon\",\n      \"pmids\": [\"2643112\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Bacterial operon regulation does not extend to eukaryotic RPL14\", \"No direct test of S8–L14 mRNA contact in vivo structure\"]\n    },\n    {\n      \"year\": 1994,\n      \"claim\": \"Identified a candidate transcription factor (FIII/YY1) binding the RPL14 promoter first exon, addressing how the gene might be transcriptionally controlled.\",\n      \"evidence\": \"cDNA cloning, oocyte overexpression, immunological characterization, and DNA-binding assays in Xenopus\",\n      \"pmids\": [\"7802655\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Binding alone did not establish a regulatory role\", \"No demonstration of effect on transcription\"]\n    },\n    {\n      \"year\": 1996,\n      \"claim\": \"Provided the atomic-level architecture of L14, defining the beta-barrel fold and mapping the surfaces that mediate rRNA contacts and a putative L19 interaction.\",\n      \"evidence\": \"X-ray crystallography (isomorphous replacement/MAD) of L14 from Bacillus stearothermophilus with surface patch analysis\",\n      \"pmids\": [\"8805509\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Bacterial structure lacks the eukaryote-specific C-terminal extension\", \"L19 interaction proposed from surface analysis, not directly co-crystallized\"]\n    },\n    {\n      \"year\": 1996,\n      \"claim\": \"Characterized the human RPL14 transcript and protein, defining domains including nuclear targeting sequences, an rRNA-binding element, and a polyalanine tract.\",\n      \"evidence\": \"cDNA cloning/sequencing from a human endothelial library with Northern blot and bioinformatic domain analysis\",\n      \"pmids\": [\"9480843\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional assays of the predicted domains\", \"Role of the polyalanine tract unknown\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Demonstrated that RPL14 is haploinsufficient and dosage-sensitive in a metazoan, linking reduced gene dosage to a defined developmental Minute phenotype.\",\n      \"evidence\": \"Drosophila P-element insertion with quantitative Northern blot and P-element remobilization rescue\",\n      \"pmids\": [\"9236770\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular basis of the Minute phenotype at the ribosome level not resolved\", \"No human disease link established here\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Resolved the FIII/YY1 question with a negative result, showing the binding sites are dispensable for RPL14 promoter activity.\",\n      \"evidence\": \"CAT reporter assays with mutated FIII/YY1 sites in Xenopus oocytes and kidney cells plus FIII/YY1 overexpression\",\n      \"pmids\": [\"9738894\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Actual cis-elements driving RPL14 transcription not identified\", \"Limited to Xenopus reporter systems\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Identified RPL14 as an SLE-specific autoantigen, raising the question of why a ribosomal protein becomes immunogenic in autoimmunity.\",\n      \"evidence\": \"2D gel/immunoblot antigen identification and recombinant GST-L14 immunoblotting against 126 SLE and 212 control sera\",\n      \"pmids\": [\"12051391\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of immunogenicity unexplored\", \"No causal link between autoantibody and disease pathology\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Confirmed that RPL14 is essential for viability and proliferation when reduced below ~50%, reinforcing its dosage-critical role across tissues.\",\n      \"evidence\": \"Spatiotemporal GAL4/UAS RNAi knockdown in Drosophila with RNA-level verification and phenotypic analysis\",\n      \"pmids\": [\"14597387\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not distinguish ribosome-assembly defects from extra-ribosomal effects\", \"No molecular pathway dissection\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Provided functional genetic evidence for the L14–L19 interaction predicted structurally, linking it to translational decoding accuracy.\",\n      \"evidence\": \"Compensatory-evolution serial passage in Salmonella with fitness, UGA read-through, and aminoglycoside sensitivity assays\",\n      \"pmids\": [\"17157877\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Bacterial context; eukaryotic L14–L19 contact not directly tested here\", \"Mechanism of decoding modulation not resolved at atomic level\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Placed eL14 in the ribosome biogenesis pathway, showing it acts early in nucleolar pre-60S assembly to drive 27S pre-rRNA processing, pre-60S export, and neighbor-protein loading, with the C-terminal extension tuning translation fidelity.\",\n      \"evidence\": \"Conditional depletion in S. cerevisiae with Northern blot of pre-rRNA intermediates, sucrose gradient sedimentation, factor co-sedimentation, and C-terminal truncation mutants\",\n      \"pmids\": [\"29788267\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct structural snapshot of eL14 within human pre-60S not provided\", \"Precise mechanism by which the C-terminal extension affects fidelity unresolved\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Linked RPL14 levels to cancer cell behavior, showing overexpression suppresses proliferation, migration, invasion, and EMT in nasopharyngeal carcinoma.\",\n      \"evidence\": \"Gain-of-function transfection with CCK-8, colony formation, cell cycle, transwell, and EMT-marker Western blots\",\n      \"pmids\": [\"34057029\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No rescue or epistasis to place RPL14 in a defined pathway\", \"Single tumor type; mechanism of EMT suppression unknown\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealed an extra-ribosomal regulatory axis: PRMT5-catalyzed symmetric arginine dimethylation stabilizes RPL14 and couples it to DNA damage repair and chemoresistance.\",\n      \"evidence\": \"Mass spectrometry, co-immunoprecipitation, siRNA knockdown, PRMT5 overexpression, and \\u03b3-H2AX/RAD51 Western blot/immunofluorescence in hepatocellular carcinoma cells\",\n      \"pmids\": [\"40115921\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific methylated arginine residues not mapped\", \"Mechanistic link between RPL14 and RAD51-mediated repair undefined\", \"Single lab and single tumor model\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How RPL14's structural role in 60S assembly mechanistically connects to its extra-ribosomal functions in DNA damage repair, EMT regulation, and chemoresistance remains unresolved.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structure of human eL14 within the assembled ribosome or pre-60S\", \"Unknown whether cancer phenotypes arise from altered translation or moonlighting activity\", \"PRMT5-dependent and ribosome-assembly functions not integrated in a single model\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 5]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0, 5, 10]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [1, 5]},\n      {\"term_id\": \"GO:0005730\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [1, 5]}\n    ],\n    \"complexes\": [\"60S large ribosomal subunit\", \"pre-60S particle\"],\n    \"partners\": [\"RPL19\", \"PRMT5\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}