Affinage

MRPS31

Small ribosomal subunit protein mS31 · UniProt Q92665

Round 2 corrected
Length
395 aa
Mass
45.3 kDa
Annotated
2026-04-28
82 papers in source corpus 6 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MRPS31 (mS31) is a mitochondria-specific structural protein of the small (28S) subunit of the mammalian mitoribosome, with no homologs in bacterial or cytosolic ribosomes (PMID:11279123). High-resolution cryo-EM structures place MRPS31 within the extensively remodeled small subunit head domain, and its N-terminus serves as a docking site for the mRNA delivery factor LRPPRC, forming a corridor that channels mitochondrial mRNAs to the decoding center during translation initiation (PMID:25838379, PMID:39134711). Loss of MRPS31 disrupts mitoribosome assembly, activates the mitochondrial unfolded protein response, and in hepatocellular carcinoma promotes invasiveness via COL1A1/ZEB1-mediated epithelial-to-mesenchymal transition (PMID:34772924, PMID:39410965).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2001 High

    Identifying MRPS31 as a mammalian-specific mitoribosomal component established that the 28S small subunit contains a substantial cohort of proteins absent from bacterial ribosomes, raising the question of what specialized functions these additions confer.

    Evidence LC/MS/MS sequencing of purified 28S mitoribosomal subunit proteins combined with EST database matching

    PMID:11279123

    Open questions at the time
    • No structural information on where MRPS31 sits within the small subunit
    • No functional consequence of MRPS31 loss tested
    • No interaction partners identified
  2. 2015 High

    Cryo-EM visualization of MRPS31 within the intact human mitoribosome at near-atomic resolution resolved its position in the remodeled small subunit head domain, providing the structural framework needed to understand its role in mRNA handling.

    Evidence Single-particle cryo-EM of the intact human mitoribosome at 3.5 Å resolution

    PMID:25838379

    Open questions at the time
    • Specific molecular contacts between MRPS31 and mRNA or translation factors not yet defined
    • Functional consequences of MRPS31 perturbation still untested
  3. 2021 Medium

    Demonstrating that MRPS31 deficiency disrupts whole mitoribosome assembly and enhances hepatoma invasiveness via COL1A1/ZEB1-dependent EMT established that MRPS31 loss has both organellar and oncogenic consequences.

    Evidence SCNA-driven MRPS31 suppression in hepatoma cell lines; mitoribosome assembly assays, invasion assays, and gene expression analysis

    PMID:34772924

    Open questions at the time
    • Whether the pro-invasive phenotype is a direct consequence of mitoribosome dysfunction or involves additional MRPS31 functions is unresolved
    • Findings from a single laboratory; not independently replicated
    • Mechanism connecting mitoribosome assembly failure to COL1A1/ZEB1 upregulation is unclear
  4. 2024 High

    Cryo-EM capture of the LRPPRC–SLIRP–mRNA complex docked onto the mitoribosome revealed that MRPS31's N-terminus directly contacts LRPPRC helical repeats, defining a mRNA handoff corridor and assigning MRPS31 a specific role in mitochondrial translation initiation.

    Evidence Cryo-EM of the LRPPRC-SLIRP-mRNA-mitoribosome complex; mitoribosome profiling and metabolic labeling

    PMID:39134711

    Open questions at the time
    • Whether mRNA handoff through the MRPS31–LRPPRC interface is transcript-selective is unknown
    • No mutagenesis of the MRPS31 N-terminal docking residues to confirm functional necessity
  5. 2024 Medium

    A C. elegans genetic screen identified mrps-31 loss as a specific activator of the mitochondrial unfolded protein response, confirming cross-species conservation of its essential role in mitoribosome function and linking its loss to mitochondrial proteotoxic stress.

    Evidence Forward genetic screen in C. elegans with UPRmt reporter assays and developmental phenotype analysis

    PMID:39410965

    Open questions at the time
    • Whether UPRmt activation reflects impaired mitoribosome assembly, stalled translation, or both is not distinguished
    • Mammalian UPRmt activation upon MRPS31 loss not yet demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanism by which MRPS31 loss triggers downstream transcriptional programs (e.g., EMT, UPRmt) and whether its N-terminal LRPPRC-docking function is required for mRNA selectivity during mitochondrial translation remain open questions.
  • No structure-guided mutagenesis of MRPS31 N-terminal residues contacting LRPPRC
  • No reconstituted in vitro translation assay testing MRPS31's contribution to mRNA delivery
  • Signaling cascade from mitoribosome deficiency to EMT gene activation is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005739 mitochondrion 3 GO:0005840 ribosome 3
Pathway
R-HSA-392499 Metabolism of proteins 3
Partners
LRPPRCMRPS39SLIRP
Complex memberships
mitochondrial small ribosomal subunit (28S)

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MRPS31 (MRP-S31) was identified as one of 15 mitochondria-specific proteins unique to the mammalian mitochondrial ribosome small (28S) subunit, with no homologs in bacterial, chloroplast, archaebacterial, or cytosolic ribosomes, establishing it as a structural component of the mammalian mitoribosome small subunit. Proteolytic digestion of purified 28S mitoribosomal subunits followed by LC/MS/MS peptide sequencing and EST database searching The Journal of biological chemistry High 11279123
2015 Cryo-EM structure of the intact human mitoribosome at 3.5 Å resolution revealed MRPS31 (mS31) as one of 80 extensively interconnected proteins in the mitoribosome, with the small subunit head domain and mRNA channel being highly remodeled relative to bacterial ribosomes; the structure provides the molecular framework for MRPS31's position within the mitoribosomal small subunit. Single-particle cryo-electron microscopy at 3.5 Å resolution of the intact human mitoribosome Science High 25838379
2021 MRPS31 deficiency caused by somatic copy number loss disrupts whole mitoribosome assembly in hepatoma cell lines (JHH5, HepG2, Hep3B, SNU449). MRPS31 suppression enhanced hepatoma cell invasiveness through upregulation of MMP7 and COL1A1; COL1A1 modulated invasiveness via ZEB1-mediated epithelial-to-mesenchymal transition, mechanistically linking MRPS31 loss to mitochondrial deregulation and cancer aggressiveness. Endogenous SCNA-dependent MRPS31 expression analysis in hepatoma cell lines; functional studies of mitoribosome assembly, invasion assays, gene expression analysis for MMP7, COL1A1, ZEB1 Cell death & disease Medium 34772924
2021 GST pulldown of recombinant MRPS31 from HEK293 cell lysate followed by nLC/MS/MS identified protein-protein interactions for MRPS31; network analysis revealed putative roles in tumourigenic cellular processes. Co-expression module analysis linked MRPS31 to acyl-CoA dehydrogenase interactions in fatty acid oxidation regulated by BDNF signalling, and MRPS31 was found overexpressed in breast cancer cell lines. GST fusion protein pulldown with HEK293 cell lysate followed by nLC/MS/MS; cancer cell line expression screening; co-expression module analysis Journal of biochemistry Low 34492114
2024 Cryo-EM structure of the LRPPRC-SLIRP-mRNA-mitoribosome complex showed that LRPPRC associates with mitoribosomal proteins mS39 and the N-terminus of mS31 (MRPS31) through recognition of LRPPRC helical repeats, forming a corridor for mRNA handoff to the mitoribosome. This defines MRPS31's N-terminus as a docking site for the mRNA delivery factor LRPPRC during mitochondrial translation initiation. Cryo-electron microscopy structure of LRPPRC-SLIRP-mRNA-mitoribosome complex; RNA sequencing, metabolic labeling, and mitoribosome profiling Nature structural & molecular biology High 39134711
2024 A missense mutation in C. elegans mrps-31 (encoding the mitoribosome small subunit protein S31) was identified as a unique activator of the mitochondrial unfolded protein response (UPRmt), confirming that MRPS-31 is required for normal mitoribosome function; loss of mrps-31 causes mitochondrial stress and impairs organismal development. Genetic screen in C. elegans; causality confirmed by allele characterization; UPRmt reporter assays; developmental phenotype analysis microPublication biology Medium 39410965

Source papers

Stage 0 corpus · 82 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2011 A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Molecular & cellular proteomics : MCP 749 21890473
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Ribosome. The structure of the human mitochondrial ribosome. Science (New York, N.Y.) 417 25838379
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2021 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. Cell metabolism 239 34800366
2016 Structure and Function of the Mitochondrial Ribosome. Annual review of biochemistry 217 27023846
2016 An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nature communications 211 27173435
2013 TRAF4 promotes TGF-β receptor signaling and drives breast cancer metastasis. Molecular cell 211 23973329
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2013 GRSF1 regulates RNA processing in mitochondrial RNA granules. Cell metabolism 198 23473034
2020 Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nature cell biology 194 32203420
2001 The small subunit of the mammalian mitochondrial ribosome. Identification of the full complement of ribosomal proteins present. The Journal of biological chemistry 189 11279123
2020 Expression analysis of mammalian mitochondrial ribosomal protein genes. Gene expression patterns : GEP 82 32987154
1990 Highly polymorphic minisatellite sequences: allele frequencies and mutation rates for five locus-specific probes in a Caucasian population. Journal - Forensic Science Society 61 2319227
1996 Clonal analysis of precancerous lesion of hepatocellular carcinoma. Gastroenterology 54 8690212
2024 Structural basis of LRPPRC-SLIRP-dependent translation by the mitoribosome. Nature structural & molecular biology 30 39134711
2019 Discovery of a Potent and Selective Fragment-like Inhibitor of Methyllysine Reader Protein Spindlin 1 (SPIN1). Journal of medicinal chemistry 30 31260300
1993 Population genetics of three VNTR polymorphisms in two different Spanish populations. International journal of legal medicine 29 8471542
2010 Germline minisatellite mutations in survivors of childhood and young adult cancer treated with radiation. International journal of radiation biology 26 21087171
2021 MRPS31 loss is a key driver of mitochondrial deregulation and hepatocellular carcinoma aggressiveness. Cell death & disease 24 34772924
1993 Human VNTR mutation and sex. EXS 22 8400715
2014 Identification of thyroid carcinoma related genes with mRMR and shortest path approaches. PloS one 19 24718460
1993 DNA-minisatellite mutations: recent investigations concerning distribution and impact on parentage testing. International journal of legal medicine 17 8094296
2011 NCI60 cancer cell line panel data and RNAi analysis help identify EAF2 as a modulator of simvastatin and lovastatin response in HCT-116 cells. PloS one 15 21483694
2003 Molecular genetic variation in the East Midlands, England: analysis of VNTR, STR and Alu insertion/deletion polymorphisms. Annals of human biology 14 12959895
2021 Expression and affinity purification of recombinant mammalian mitochondrial ribosomal small subunit (MRPS) proteins and protein-protein interaction analysis indicate putative role in tumourigenic cellular processes. Journal of biochemistry 13 34492114
2021 Comparison of the transcriptome in circulating leukocytes in early lactation between primiparous and multiparous cows provides evidence for age-related changes. BMC genomics 13 34563126
2014 Germline minisatellite mutations in workers occupationally exposed to radiation at the Sellafield nuclear facility. Journal of radiological protection : official journal of the Society for Radiological Protection 13 25485533
1995 Recent observations in human DNA-minisatellite mutations. International journal of legal medicine 13 7599098
1994 DNA variability and parentage testing in captive Waldrapp ibises. Molecular ecology 13 7921356
1991 Population genetic data determined for five different single locus minisatellite probes. EXS 13 1678355
2019 Functional heritage: the evolution of chimeric RNA into a gene. RNA biology 12 31566065
2006 A pilot study examining germline minisatellite mutations in the offspring of Danish childhood and adolescent cancer survivors treated with radiotherapy. International journal of radiation biology 11 16638712
1993 Paternity testing with VNTR DNA systems. I. Matching criteria and population frequencies of the VNTR systems D2S44, D5S43, D7S21, D7S22, and D12S11 in Danes. International journal of legal medicine 11 8094294
1992 Statistical analysis of the measurement errors in the determination of fragment length in DNA-RFLP analysis. Forensic science international 11 1351023
1996 Analysis of allelic structures at the D7S21 (MS31A) locus in the Japanese, using minisatellite variant repeat mapping by PCR (MVR-PCR). Annals of human genetics 8 8865988
1993 Genetic linkage analysis of thyroid autoantibodies. Autoimmunity 8 7903561
2023 Identifying the mitochondrial metabolism network by integration of machine learning and explainable artificial intelligence in skeletal muscle in type 2 diabetes. Mitochondrion 7 38040172
1992 DNA profiling in a genetically isolated population using three hypervariable DNA markers. Human heredity 7 1362961
1990 Demonstration of acquired hemizygosity and clonality in acute lymphoblastic leukemia with chromosome 7 abnormalities using hypervariable DNA probes. Genes, chromosomes & cancer 7 1980609
2020 Transcriptome and Gene Fusion Analysis of Synchronous Lesions Reveals lncMRPS31P5 as a Novel Transcript Involved in Colorectal Cancer. International journal of molecular sciences 6 32992457
1993 Paternity testing with VNTR DNA systems. II. Evaluation of 271 cases of disputed paternity with the VNTR systems D2S44, D5S43, D7S21, D7S22, and D12S11. International journal of legal medicine 6 8094295
1993 Application of human minisatellite probes to the development of informative DNA fingerprints and the isolation of locus-specific markers in animals. EXS 6 8400710
2023 A Novel Marine Mammal Coxiella burnetii-Genome Sequencing Identifies a New Genotype with Potential Virulence. Pathogens (Basel, Switzerland) 5 37513739
2022 Whole genome bisulfite sequencing reveals DNA methylation roles in the adaptive response of wildness training giant pandas to wild environment. Frontiers in genetics 5 36303550
1994 DNA polymorphism in Greenland. Allele and profile frequencies in a Greenland population sample using the VNTR probes MS1, MS31, MS43a and YNH24. International journal of legal medicine 5 7915134
1993 DNA-profiling of stains in criminal cases: analysis of measurement errors and band-shift. Discussion of match criteria. Forensic science international 5 7901133
1993 Analysis of a Danish Caucasian population sample of single locus DNA-profiles. Allele frequencies, frequencies of DNA-profiles and heterozygosity. Forensic science international 4 8101176
1993 Genetic investigations in immigration cases and frequencies of DNA fragments of the VNTR systems D2S44, D5S43, D7S21, D7S22, and D12S11 in Turks. Forensic science international 4 8101827
2001 Optimal conditions for production of (R)-1-phenylpropanol by Fusarium moniliforme strain MS31. Journal of bioscience and bioengineering 3 16233098
1995 Large scale database experiments to assess the significance of matching DNA profiles. International journal of legal medicine 3 7495691
1994 The effect of sample size on the estimation of the frequency of DNA-profiles in RFLP-analysis. Forensic science international 3 7913690
2001 Involvement of cytochrome P450 in hydroxylation of propylbenzene by Fusarium moniliforme strain MS31. Journal of bioscience and bioengineering 2 16233150
1991 [Restriction fragment study (RFLP) of DNA polymorphism in criminology: quantitative and qualitative analyses beginning with dried blood and semen on various supports]. Revue francaise de transfusion et d'hemobiologie : bulletin de la Societe nationale de transfusion sanguine 2 1674416
2025 Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma. International journal of molecular sciences 1 39859203
2024 A viable hypomorphic mutation in the mitochondrial ribosome subunit, MRPS-31, exhibits mitochondrial dysfunction in C. elegans. microPublication biology 1 39410965
2007 [The effects of chronic radiation exposure on the frequency of mutations at minisatellite DNA loci in residents of the Techa Riverside Villages]. Radiatsionnaia biologiia, radioecologiia 1 18051681
2025 Molecular mechanism of interactions of SPIN1 with novel inhibitors through molecular docking and molecular dynamics simulations. SAR and QSAR in environmental research 0 39989297
2025 Immune-modulatory effects of Spindlin-1 inhibitors. Clinical and experimental immunology 0 40512144
1995 [Follow-up of allogenic bone marrow graft with DNA polymorphisms. Use of two minisatellite MS31 and MS43 probes. Comparison with data of chromosomal polymorphisms]. Presse medicale (Paris, France : 1983) 0 7770390
1995 A validation study of four single locus probes (MS1, MS31, MS43 and g3) in a Korean population--further evaluation for paternity testing. Journal of Korean medical science 0 8593203
1993 [Measuring precision in determining the length of restriction fragments within the scope of DNA analysis]. Archiv fur Kriminologie 0 8099786
1992 Comparison of two molecular weight markers used in DNA-profiling. International journal of legal medicine 0 1358177
1991 [The use of highly polymorphic DNA systems in the demonstration of mixed chimerism following bone marrow transplantation]. Wiener klinische Wochenschrift 0 1674392