{"gene":"MRPL48","run_date":"2026-06-10T02:59:51","timeline":{"discoveries":[{"year":2020,"finding":"Cryo-EM structures of the human mitoribosome at ~3.0 Å resolution, including eight functional complexes, revealed that mitoribosomal large subunit protein mL48 (MRPL48), together with mL40 and mL64, coordinates translocation of mt-tRNA during the elongation cycle.","method":"Cryo-EM structure determination of human mitoribosome in functional complexes (with mt-mRNA, mt-tRNAs, recycling factor, and trans factors)","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1 / Strong — high-resolution cryo-EM structures with multiple functional states resolved in a single rigorous study","pmids":["32812867"],"is_preprint":false},{"year":2010,"finding":"The C-terminal tail of human Oxa1L (Oxa1L-CTT) physically cross-links to MRPL48 (along with MRPL49 and MRPL51) on the mitochondrial large ribosomal subunit, positioning MRPL48 at or near the mitoribosome surface contacted by Oxa1L during co-translational membrane insertion.","method":"Chemical cross-linking followed by mass spectrometry / protein identification; ribosome-binding assays with purified Oxa1L-CTT","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct cross-linking experiment with purified components, single lab, two complementary methods (cross-linking + binding affinity measurement)","pmids":["20601428"],"is_preprint":false},{"year":2020,"finding":"CRISPR-Cas9 knockout of MRPL48 in Caco-2 colorectal cancer cells enhanced sensitivity to cetuximab, as validated by colony formation and CCK-8 cell viability assays, identifying MRPL48 as a mediator of cetuximab resistance.","method":"CRISPR-Cas9 gene knockout; colony formation assay; CCK-8 cell viability assay","journal":"Bioscience reports","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KO with defined cellular phenotype, single lab, no molecular pathway placement beyond drug sensitivity","pmids":["33048115"],"is_preprint":false}],"current_model":"MRPL48 (mL48) is a protein of the mitochondrial large ribosomal subunit that coordinates mt-tRNA translocation during mitochondrial translation, physically contacts the Oxa1L C-terminal tail to facilitate co-translational membrane insertion of mitochondria-synthesized proteins, and whose loss confers cetuximab sensitivity in colorectal cancer cells."},"narrative":{"mechanistic_narrative":"MRPL48 (mL48) is a protein component of the mitochondrial large ribosomal subunit that participates in mitochondrial translation [PMID:32812867]. Within the mitoribosome, mL48 acts together with mL40 and mL64 to coordinate translocation of mt-tRNA during the elongation cycle [PMID:32812867]. Its C-terminal location near the mitoribosome surface places it in contact with the C-terminal tail of Oxa1L, linking the elongating ribosome to the co-translational membrane insertion of mitochondrially synthesized proteins [PMID:20601428]. Loss of MRPL48 by CRISPR-Cas9 knockout sensitizes colorectal cancer cells to cetuximab, identifying it as a mediator of cetuximab resistance, though the molecular pathway connecting mitochondrial translation to drug response has not been characterized in the available corpus [PMID:33048115].","teleology":[{"year":2010,"claim":"Establishing how nascent mitochondrial proteins are handed from the ribosome to the membrane insertase, this work showed the Oxa1L C-terminal tail physically engages MRPL48 on the large subunit, positioning it at the ribosome-insertase interface.","evidence":"Chemical cross-linking with mass spectrometry and ribosome-binding assays using purified Oxa1L-CTT","pmids":["20601428"],"confidence":"Medium","gaps":["Cross-linking alone does not define a direct binary interaction versus proximity within the assembled subunit","Functional consequence of disrupting the MRPL48-Oxa1L contact for membrane insertion not tested","Whether mL49 and mL51 or mL48 forms the principal contact is unresolved"]},{"year":2020,"claim":"Resolving the structural role of mL48 in active translation, high-resolution cryo-EM of functional mitoribosome states placed mL48 with mL40 and mL64 at a site coordinating mt-tRNA translocation during elongation.","evidence":"Cryo-EM structure determination of human mitoribosome in eight functional complexes with mt-mRNA, mt-tRNAs and trans factors","pmids":["32812867"],"confidence":"High","gaps":["Structural assignment does not define the kinetic contribution of mL48 to translocation","No mutational test of mL48's role in tRNA handling"]},{"year":2020,"claim":"Connecting mitoribosomal function to a cancer drug response, knockout of MRPL48 was shown to enhance cetuximab sensitivity, implicating it in cetuximab resistance of colorectal cancer cells.","evidence":"CRISPR-Cas9 knockout in Caco-2 cells with colony formation and CCK-8 viability assays","pmids":["33048115"],"confidence":"Medium","gaps":["No molecular pathway links mitochondrial translation to cetuximab response","Phenotype shown in a single cell line without in vivo validation","Whether the effect depends on mL48's translational role is untested"]},{"year":null,"claim":"How mL48's role in mt-tRNA translocation and its contact with Oxa1L mechanistically connect to cetuximab resistance remains unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No mechanistic bridge between mitochondrial translation defects and EGFR-pathway drug sensitivity established","No structural or functional consequence of mL48 loss on co-translational membrane insertion demonstrated"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[0,1]}],"pathway":[{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0]}],"complexes":["mitochondrial large ribosomal subunit"],"partners":["OXA1L"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q96GC5","full_name":"Large ribosomal subunit protein mL48","aliases":["39S ribosomal protein L48, mitochondrial","L48mt","MRP-L48"],"length_aa":212,"mass_kda":23.9,"function":"","subcellular_location":"Mitochondrion","url":"https://www.uniprot.org/uniprotkb/Q96GC5/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/MRPL48","classification":"Not Classified","n_dependent_lines":245,"n_total_lines":1208,"dependency_fraction":0.20281456953642385},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"IGF2BP1","stoichiometry":0.2},{"gene":"LSM14A","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/MRPL48","total_profiled":1310},"omim":[{"mim_id":"611853","title":"MITOCHONDRIAL RIBOSOMAL PROTEIN L48; MRPL48","url":"https://www.omim.org/entry/611853"},{"mim_id":"608707","title":"CELL ADHESION MOLECULE-RELATED/DOWNREGULATED BY ONCOGENES; CDON","url":"https://www.omim.org/entry/608707"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Mitochondria","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/MRPL48"},"hgnc":{"alias_symbol":["CGI-118","mL48"],"prev_symbol":[]},"alphafold":{"accession":"Q96GC5","domains":[{"cath_id":"3.30.70.600","chopping":"88-136_150-212","consensus_level":"high","plddt":90.8248,"start":88,"end":212}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96GC5","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96GC5-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96GC5-F1-predicted_aligned_error_v6.png","plddt_mean":76.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=MRPL48","jax_strain_url":"https://www.jax.org/strain/search?query=MRPL48"},"sequence":{"accession":"Q96GC5","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96GC5.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96GC5/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96GC5"}},"corpus_meta":[{"pmid":"32812867","id":"PMC_32812867","title":"Structural basis 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\"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"Cryo-EM structures of the human mitoribosome at ~3.0 Å resolution, including eight functional complexes, revealed that mitoribosomal large subunit protein mL48 (MRPL48), together with mL40 and mL64, coordinates translocation of mt-tRNA during the elongation cycle.\",\n      \"method\": \"Cryo-EM structure determination of human mitoribosome in functional complexes (with mt-mRNA, mt-tRNAs, recycling factor, and trans factors)\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — high-resolution cryo-EM structures with multiple functional states resolved in a single rigorous study\",\n      \"pmids\": [\"32812867\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"The C-terminal tail of human Oxa1L (Oxa1L-CTT) physically cross-links to MRPL48 (along with MRPL49 and MRPL51) on the mitochondrial large ribosomal subunit, positioning MRPL48 at or near the mitoribosome surface contacted by Oxa1L during co-translational membrane insertion.\",\n      \"method\": \"Chemical cross-linking followed by mass spectrometry / protein identification; ribosome-binding assays with purified Oxa1L-CTT\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct cross-linking experiment with purified components, single lab, two complementary methods (cross-linking + binding affinity measurement)\",\n      \"pmids\": [\"20601428\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"CRISPR-Cas9 knockout of MRPL48 in Caco-2 colorectal cancer cells enhanced sensitivity to cetuximab, as validated by colony formation and CCK-8 cell viability assays, identifying MRPL48 as a mediator of cetuximab resistance.\",\n      \"method\": \"CRISPR-Cas9 gene knockout; colony formation assay; CCK-8 cell viability assay\",\n      \"journal\": \"Bioscience reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KO with defined cellular phenotype, single lab, no molecular pathway placement beyond drug sensitivity\",\n      \"pmids\": [\"33048115\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"MRPL48 (mL48) is a protein of the mitochondrial large ribosomal subunit that coordinates mt-tRNA translocation during mitochondrial translation, physically contacts the Oxa1L C-terminal tail to facilitate co-translational membrane insertion of mitochondria-synthesized proteins, and whose loss confers cetuximab sensitivity in colorectal cancer cells.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"MRPL48 (mL48) is a protein component of the mitochondrial large ribosomal subunit that participates in mitochondrial translation [#0]. Within the mitoribosome, mL48 acts together with mL40 and mL64 to coordinate translocation of mt-tRNA during the elongation cycle [#0]. Its C-terminal location near the mitoribosome surface places it in contact with the C-terminal tail of Oxa1L, linking the elongating ribosome to the co-translational membrane insertion of mitochondrially synthesized proteins [#1]. Loss of MRPL48 by CRISPR-Cas9 knockout sensitizes colorectal cancer cells to cetuximab, identifying it as a mediator of cetuximab resistance, though the molecular pathway connecting mitochondrial translation to drug response has not been characterized in the available corpus [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Establishing how nascent mitochondrial proteins are handed from the ribosome to the membrane insertase, this work showed the Oxa1L C-terminal tail physically engages MRPL48 on the large subunit, positioning it at the ribosome-insertase interface.\",\n      \"evidence\": \"Chemical cross-linking with mass spectrometry and ribosome-binding assays using purified Oxa1L-CTT\",\n      \"pmids\": [\"20601428\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Cross-linking alone does not define a direct binary interaction versus proximity within the assembled subunit\",\n        \"Functional consequence of disrupting the MRPL48-Oxa1L contact for membrane insertion not tested\",\n        \"Whether mL49 and mL51 or mL48 forms the principal contact is unresolved\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Resolving the structural role of mL48 in active translation, high-resolution cryo-EM of functional mitoribosome states placed mL48 with mL40 and mL64 at a site coordinating mt-tRNA translocation during elongation.\",\n      \"evidence\": \"Cryo-EM structure determination of human mitoribosome in eight functional complexes with mt-mRNA, mt-tRNAs and trans factors\",\n      \"pmids\": [\"32812867\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Structural assignment does not define the kinetic contribution of mL48 to translocation\",\n        \"No mutational test of mL48's role in tRNA handling\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connecting mitoribosomal function to a cancer drug response, knockout of MRPL48 was shown to enhance cetuximab sensitivity, implicating it in cetuximab resistance of colorectal cancer cells.\",\n      \"evidence\": \"CRISPR-Cas9 knockout in Caco-2 cells with colony formation and CCK-8 viability assays\",\n      \"pmids\": [\"33048115\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No molecular pathway links mitochondrial translation to cetuximab response\",\n        \"Phenotype shown in a single cell line without in vivo validation\",\n        \"Whether the effect depends on mL48's translational role is untested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How mL48's role in mt-tRNA translocation and its contact with Oxa1L mechanistically connect to cetuximab resistance remains unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No mechanistic bridge between mitochondrial translation defects and EGFR-pathway drug sensitivity established\",\n        \"No structural or functional consequence of mL48 loss on co-translational membrane insertion demonstrated\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"mitochondrial large ribosomal subunit\"],\n    \"partners\": [\"OXA1L\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}