{"gene":"MRPS31","run_date":"2026-06-10T02:59:51","timeline":{"discoveries":[{"year":2024,"finding":"MRPS31 (mS31) is a component of the mitoribosomal small subunit and its N-terminus physically interacts with the mRNA delivery factor LRPPRC, as shown by cryo-EM structure of the LRPPRC-SLIRP-mRNA-mitoribosome complex. LRPPRC helical repeats recognize mS39 and the N-terminus of mS31, forming a corridor for mRNA handoff to the mitoribosome.","method":"Cryo-electron microscopy structural determination of the LRPPRC-SLIRP-mRNA-mitoribosome complex, combined with RNA sequencing, metabolic labeling, and mitoribosome profiling","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — cryo-EM structure with direct identification of binding interface, supported by multiple orthogonal functional assays in a single rigorous study","pmids":["39134711"],"is_preprint":false},{"year":2021,"finding":"MRPS31 deficiency disrupts whole mitoribosome assembly in hepatoma cell lines with somatic copy number alteration-dependent MRPS31 expression. Loss of MRPS31 also enhances hepatoma cell invasiveness by augmenting MMP7 and COL1A1 expression, with COL1A1 modulating invasiveness via ZEB1-mediated epithelial-to-mesenchymal transition.","method":"Loss-of-function analysis using hepatoma cell lines with SCNA-dependent MRPS31 expression (JHH5, HepG2, Hep3B, SNU449); mitoribosome assembly assays; invasion assays; gene expression analysis","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO/KD with defined cellular phenotype and pathway placement (mitoribosome assembly, EMT via ZEB1), single lab with multiple orthogonal readouts","pmids":["34772924"],"is_preprint":false},{"year":2021,"finding":"GST-pulldown of MRPS31 fusion protein from HEK293 cell lysate followed by nLC/MS/MS identified protein-protein interactions for MRPS31, with PPI network analysis suggesting putative roles in tumourigenic cellular processes including fatty acid oxidation. MRPS31 was also found to be overexpressed in breast cancer cell lines.","method":"GST pulldown using recombinant GST-MRPS31 fusion protein and HEK293 cell lysate, followed by nLC/MS/MS mass spectrometry analysis; cancer cell line gene expression screening","journal":"Journal of biochemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single GST pulldown with mass spectrometry, single lab, no functional validation of MRPS31-specific interactions reported","pmids":["34492114"],"is_preprint":false},{"year":2024,"finding":"A missense mutation in C. elegans mrps-31 (encoding the mitoribosome small subunit protein S31) causes mitochondrial unfolded protein response (UPRmt) activation and impairs organismal development, confirming that MRPS-31 is required for normal mitoribosome function and mitochondrial protein homeostasis.","method":"Forward genetic screen in C. elegans; causality confirmed by genetic complementation; UPRmt reporter assays; developmental phenotype characterization","journal":"microPublication biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined cellular phenotype (UPRmt induction, developmental defects) in C. elegans ortholog, causality confirmed, single lab","pmids":["39410965"],"is_preprint":false}],"current_model":"MRPS31 (mS31) is a structural component of the mitoribosomal small subunit whose N-terminus directly contacts the mRNA delivery factor LRPPRC (as revealed by cryo-EM), forming a corridor for mitochondrial mRNA handoff during translation; loss of MRPS31 disrupts mitoribosome assembly, activates mitochondrial stress responses, and in hepatocellular carcinoma promotes invasiveness via MMP7 and ZEB1-mediated EMT."},"narrative":{"mechanistic_narrative":"MRPS31 (mS31) is a structural protein of the mitochondrial small ribosomal subunit that links mitoribosome assembly to mitochondrial mRNA delivery during translation [PMID:39134711]. Cryo-EM of the LRPPRC–SLIRP–mRNA–mitoribosome complex shows that the N-terminus of mS31 is directly recognized by the LRPPRC helical repeats, together with mS39, forming a corridor that hands off mitochondrial mRNA to the small subunit [PMID:39134711]. Consistent with this structural role, loss of MRPS31 disrupts assembly of the whole mitoribosome and impairs mitochondrial protein homeostasis: depletion in hepatoma cells blocks mitoribosome assembly [PMID:34772924], and a missense mutation in the C. elegans ortholog activates the mitochondrial unfolded protein response and impairs development [PMID:39410965]. In hepatocellular carcinoma, MRPS31 loss enhances cell invasiveness by augmenting MMP7 and COL1A1 expression, with COL1A1 driving invasiveness through ZEB1-mediated epithelial-to-mesenchymal transition [PMID:34772924]. Beyond its role in mitoribosomal assembly and mRNA handoff, no additional catalytic or regulatory mechanism for MRPS31 has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"Whether MRPS31 is functionally required for mitoribosome assembly—and whether its loss has cellular consequences in cancer—was unresolved; this established MRPS31 as essential for mitoribosome assembly and as a modulator of tumor cell invasiveness.","evidence":"Loss-of-function (KO/KD) in hepatoma cell lines with SCNA-dependent MRPS31 expression, mitoribosome assembly assays, invasion and gene-expression analysis","pmids":["34772924"],"confidence":"Medium","gaps":["Mechanism linking mitoribosome disruption to upregulation of MMP7/COL1A1 not defined","Direct structural role of MRPS31 in the ribosome not addressed","Single-lab cellular system"]},{"year":2021,"claim":"The physical interaction partners of MRPS31 outside the mitoribosome were unknown; a pulldown screen catalogued putative interactions and noted overexpression in breast cancer, hinting at broader cellular associations.","evidence":"GST-pulldown of recombinant GST-MRPS31 from HEK293 lysate with nLC/MS/MS, plus cancer cell line expression screening","pmids":["34492114"],"confidence":"Low","gaps":["Single GST pulldown without functional validation of any MRPS31-specific interaction","Putative roles (e.g., fatty acid oxidation) inferred from network analysis, not tested","No reciprocal validation"]},{"year":2024,"claim":"How MRPS31 connects to mitochondrial mRNA delivery at the structural level was unknown; cryo-EM established direct contact between the mS31 N-terminus and LRPPRC, defining a corridor for mRNA handoff to the mitoribosome.","evidence":"Cryo-EM of the LRPPRC-SLIRP-mRNA-mitoribosome complex with RNA-seq, metabolic labeling, and mitoribosome profiling","pmids":["39134711"],"confidence":"High","gaps":["Functional contribution of the mS31 N-terminus to mRNA handoff not isolated by mutagenesis","Dynamics/kinetics of the handoff not resolved","Conservation of the interface across species not addressed"]},{"year":2024,"claim":"Whether MRPS31 function and its requirement for mitochondrial proteostasis are conserved in a whole organism was untested; an ortholog mutant established that MRPS-31 is required for normal mitoribosome function and triggers UPRmt when lost.","evidence":"Forward genetic screen and complementation in C. elegans, UPRmt reporter assays, developmental phenotyping","pmids":["39410965"],"confidence":"Medium","gaps":["Molecular step in mitoribosome function disrupted by the missense allele not defined","Link between UPRmt and developmental defects not mechanistically dissected"]},{"year":null,"claim":"How MRPS31 deficiency mechanistically couples mitoribosome/mitochondrial stress to the EMT and invasion program (MMP7, COL1A1, ZEB1) remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Signaling pathway from mitoribosome disruption to ZEB1-mediated EMT undefined","Whether the invasion phenotype is mitochondria-dependent untested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]},{"term_id":"GO:0003723","term_label":"RNA binding","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,3]},{"term_id":"GO:0005840","term_label":"ribosome","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,1]}],"complexes":["mitochondrial small ribosomal subunit (mitoribosome)"],"partners":["LRPPRC","SLIRP","MRPS39"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q92665","full_name":"Small ribosomal subunit protein mS31","aliases":["28S ribosomal protein S31, mitochondrial","MRP-S31","S31mt","Imogen 38"],"length_aa":395,"mass_kda":45.3,"function":"","subcellular_location":"Mitochondrion","url":"https://www.uniprot.org/uniprotkb/Q92665/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/MRPS31","classification":"Common Essential","n_dependent_lines":632,"n_total_lines":1208,"dependency_fraction":0.5231788079470199},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HNRNPL","stoichiometry":0.2},{"gene":"RBM39","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MRPS31","total_profiled":1310},"omim":[{"mim_id":"611992","title":"MITOCHONDRIAL RIBOSOMAL PROTEIN S31; MRPS31","url":"https://www.omim.org/entry/611992"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Mitochondria","reliability":"Supported"},{"location":"Nucleoli","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MRPS31"},"hgnc":{"alias_symbol":["IMOGN38","mS31"],"prev_symbol":[]},"alphafold":{"accession":"Q92665","domains":[{"cath_id":"-","chopping":"326-391","consensus_level":"high","plddt":91.9047,"start":326,"end":391},{"cath_id":"1.10.287","chopping":"154-194","consensus_level":"high","plddt":87.8012,"start":154,"end":194}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92665","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q92665-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q92665-F1-predicted_aligned_error_v6.png","plddt_mean":66.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MRPS31","jax_strain_url":"https://www.jax.org/strain/search?query=MRPS31"},"sequence":{"accession":"Q92665","fasta_url":"https://rest.uniprot.org/uniprotkb/Q92665.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q92665/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q92665"}},"corpus_meta":[{"pmid":"2319227","id":"PMC_2319227","title":"Highly 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Comparison with data of chromosomal polymorphisms].","date":"1995","source":"Presse medicale (Paris, France : 1983)","url":"https://pubmed.ncbi.nlm.nih.gov/7770390","citation_count":0,"is_preprint":false},{"pmid":"40512144","id":"PMC_40512144","title":"Immune-modulatory effects of Spindlin-1 inhibitors.","date":"2025","source":"Clinical and experimental immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40512144","citation_count":0,"is_preprint":false},{"pmid":"1358177","id":"PMC_1358177","title":"Comparison of two molecular weight markers used in DNA-profiling.","date":"1992","source":"International journal of legal medicine","url":"https://pubmed.ncbi.nlm.nih.gov/1358177","citation_count":0,"is_preprint":false},{"pmid":"39989297","id":"PMC_39989297","title":"Molecular mechanism of interactions of SPIN1 with novel inhibitors through molecular docking and molecular dynamics simulations.","date":"2025","source":"SAR and QSAR in environmental research","url":"https://pubmed.ncbi.nlm.nih.gov/39989297","citation_count":0,"is_preprint":false},{"pmid":"1674392","id":"PMC_1674392","title":"[The use of highly polymorphic DNA systems in the demonstration of mixed chimerism following bone marrow transplantation].","date":"1991","source":"Wiener klinische Wochenschrift","url":"https://pubmed.ncbi.nlm.nih.gov/1674392","citation_count":0,"is_preprint":false},{"pmid":"8099786","id":"PMC_8099786","title":"[Measuring precision in determining the length of restriction fragments within the scope of DNA analysis].","date":"1993","source":"Archiv fur Kriminologie","url":"https://pubmed.ncbi.nlm.nih.gov/8099786","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":22384,"output_tokens":1170,"usd":0.042351,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7788,"output_tokens":2095,"usd":0.045657,"stage2_stop_reason":"end_turn"},"total_usd":0.088008,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"MRPS31 (mS31) is a component of the mitoribosomal small subunit and its N-terminus physically interacts with the mRNA delivery factor LRPPRC, as shown by cryo-EM structure of the LRPPRC-SLIRP-mRNA-mitoribosome complex. LRPPRC helical repeats recognize mS39 and the N-terminus of mS31, forming a corridor for mRNA handoff to the mitoribosome.\",\n      \"method\": \"Cryo-electron microscopy structural determination of the LRPPRC-SLIRP-mRNA-mitoribosome complex, combined with RNA sequencing, metabolic labeling, and mitoribosome profiling\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — cryo-EM structure with direct identification of binding interface, supported by multiple orthogonal functional assays in a single rigorous study\",\n      \"pmids\": [\"39134711\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"MRPS31 deficiency disrupts whole mitoribosome assembly in hepatoma cell lines with somatic copy number alteration-dependent MRPS31 expression. Loss of MRPS31 also enhances hepatoma cell invasiveness by augmenting MMP7 and COL1A1 expression, with COL1A1 modulating invasiveness via ZEB1-mediated epithelial-to-mesenchymal transition.\",\n      \"method\": \"Loss-of-function analysis using hepatoma cell lines with SCNA-dependent MRPS31 expression (JHH5, HepG2, Hep3B, SNU449); mitoribosome assembly assays; invasion assays; gene expression analysis\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO/KD with defined cellular phenotype and pathway placement (mitoribosome assembly, EMT via ZEB1), single lab with multiple orthogonal readouts\",\n      \"pmids\": [\"34772924\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"GST-pulldown of MRPS31 fusion protein from HEK293 cell lysate followed by nLC/MS/MS identified protein-protein interactions for MRPS31, with PPI network analysis suggesting putative roles in tumourigenic cellular processes including fatty acid oxidation. MRPS31 was also found to be overexpressed in breast cancer cell lines.\",\n      \"method\": \"GST pulldown using recombinant GST-MRPS31 fusion protein and HEK293 cell lysate, followed by nLC/MS/MS mass spectrometry analysis; cancer cell line gene expression screening\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single GST pulldown with mass spectrometry, single lab, no functional validation of MRPS31-specific interactions reported\",\n      \"pmids\": [\"34492114\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A missense mutation in C. elegans mrps-31 (encoding the mitoribosome small subunit protein S31) causes mitochondrial unfolded protein response (UPRmt) activation and impairs organismal development, confirming that MRPS-31 is required for normal mitoribosome function and mitochondrial protein homeostasis.\",\n      \"method\": \"Forward genetic screen in C. elegans; causality confirmed by genetic complementation; UPRmt reporter assays; developmental phenotype characterization\",\n      \"journal\": \"microPublication biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotype (UPRmt induction, developmental defects) in C. elegans ortholog, causality confirmed, single lab\",\n      \"pmids\": [\"39410965\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MRPS31 (mS31) is a structural component of the mitoribosomal small subunit whose N-terminus directly contacts the mRNA delivery factor LRPPRC (as revealed by cryo-EM), forming a corridor for mitochondrial mRNA handoff during translation; loss of MRPS31 disrupts mitoribosome assembly, activates mitochondrial stress responses, and in hepatocellular carcinoma promotes invasiveness via MMP7 and ZEB1-mediated EMT.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MRPS31 (mS31) is a structural protein of the mitochondrial small ribosomal subunit that links mitoribosome assembly to mitochondrial mRNA delivery during translation [#0]. Cryo-EM of the LRPPRC–SLIRP–mRNA–mitoribosome complex shows that the N-terminus of mS31 is directly recognized by the LRPPRC helical repeats, together with mS39, forming a corridor that hands off mitochondrial mRNA to the small subunit [#0]. Consistent with this structural role, loss of MRPS31 disrupts assembly of the whole mitoribosome and impairs mitochondrial protein homeostasis: depletion in hepatoma cells blocks mitoribosome assembly [#1], and a missense mutation in the C. elegans ortholog activates the mitochondrial unfolded protein response and impairs development [#3]. In hepatocellular carcinoma, MRPS31 loss enhances cell invasiveness by augmenting MMP7 and COL1A1 expression, with COL1A1 driving invasiveness through ZEB1-mediated epithelial-to-mesenchymal transition [#1]. Beyond its role in mitoribosomal assembly and mRNA handoff, no additional catalytic or regulatory mechanism for MRPS31 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether MRPS31 is functionally required for mitoribosome assembly—and whether its loss has cellular consequences in cancer—was unresolved; this established MRPS31 as essential for mitoribosome assembly and as a modulator of tumor cell invasiveness.\",\n      \"evidence\": \"Loss-of-function (KO/KD) in hepatoma cell lines with SCNA-dependent MRPS31 expression, mitoribosome assembly assays, invasion and gene-expression analysis\",\n      \"pmids\": [\"34772924\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism linking mitoribosome disruption to upregulation of MMP7/COL1A1 not defined\",\n        \"Direct structural role of MRPS31 in the ribosome not addressed\",\n        \"Single-lab cellular system\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"The physical interaction partners of MRPS31 outside the mitoribosome were unknown; a pulldown screen catalogued putative interactions and noted overexpression in breast cancer, hinting at broader cellular associations.\",\n      \"evidence\": \"GST-pulldown of recombinant GST-MRPS31 from HEK293 lysate with nLC/MS/MS, plus cancer cell line expression screening\",\n      \"pmids\": [\"34492114\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single GST pulldown without functional validation of any MRPS31-specific interaction\",\n        \"Putative roles (e.g., fatty acid oxidation) inferred from network analysis, not tested\",\n        \"No reciprocal validation\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"How MRPS31 connects to mitochondrial mRNA delivery at the structural level was unknown; cryo-EM established direct contact between the mS31 N-terminus and LRPPRC, defining a corridor for mRNA handoff to the mitoribosome.\",\n      \"evidence\": \"Cryo-EM of the LRPPRC-SLIRP-mRNA-mitoribosome complex with RNA-seq, metabolic labeling, and mitoribosome profiling\",\n      \"pmids\": [\"39134711\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Functional contribution of the mS31 N-terminus to mRNA handoff not isolated by mutagenesis\",\n        \"Dynamics/kinetics of the handoff not resolved\",\n        \"Conservation of the interface across species not addressed\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Whether MRPS31 function and its requirement for mitochondrial proteostasis are conserved in a whole organism was untested; an ortholog mutant established that MRPS-31 is required for normal mitoribosome function and triggers UPRmt when lost.\",\n      \"evidence\": \"Forward genetic screen and complementation in C. elegans, UPRmt reporter assays, developmental phenotyping\",\n      \"pmids\": [\"39410965\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular step in mitoribosome function disrupted by the missense allele not defined\",\n        \"Link between UPRmt and developmental defects not mechanistically dissected\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How MRPS31 deficiency mechanistically couples mitoribosome/mitochondrial stress to the EMT and invasion program (MMP7, COL1A1, ZEB1) remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Signaling pathway from mitoribosome disruption to ZEB1-mediated EMT undefined\",\n        \"Whether the invasion phenotype is mitochondria-dependent untested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0003723\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0005840\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\"mitochondrial small ribosomal subunit (mitoribosome)\"],\n    \"partners\": [\"LRPPRC\", \"SLIRP\", \"MRPS39\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":4,"faith_total":4,"faith_pct":100.0}}