Affinage

MRPL51

Large ribosomal subunit protein mL51 · UniProt Q4U2R6

Round 2 corrected
Length
128 aa
Mass
15.1 kDa
Annotated
2026-04-28
41 papers in source corpus 12 papers cited in narrative 12 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MRPL51 is an essential structural component of the 39S large subunit of the mammalian mitochondrial ribosome, where it occupies a surface-exposed position that mediates direct interaction with the C-terminal tail of the inner membrane insertase Oxa1L during co-translational insertion of mitochondrially encoded membrane proteins (PMID:11551941, PMID:20601428). High-resolution cryo-EM structures have resolved MRPL51 within the mature mt-LSU and within late-stage assembly intermediates, revealing the timing of its incorporation during ribosomal maturation (PMID:25278503, PMID:28892042). In yeast, the MRPL51 ortholog has an additional Mhr1-dependent role in mitochondrial DNA maintenance, and in mammalian cells MRPL51 knockdown attenuates oxygen-glucose deprivation-induced apoptosis and suppresses epithelial–mesenchymal transition in lung adenocarcinoma downstream of FOXM1 transcriptional activation (PMID:31374566, PMID:32618081, PMID:37323822). MRPL51 is individually essential for early embryonic development in mice, consistent with non-redundant roles among mitoribosomal proteins (PMID:32987154).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2001 High

    Establishing MRPL51 as a bona fide constituent of the mammalian mitoribosome resolved its molecular identity and placed it within the 48-protein mt-LSU, answering whether it was a genuine ribosomal protein rather than a contaminant or accessory factor.

    Evidence Proteolytic digestion of purified 39S subunits with LC-MS/MS peptide identification; parallel chromosomal mapping by radiation hybrid panel

    PMID:11543634 PMID:11551941

    Open questions at the time
    • No information on MRPL51's position within the subunit or contacts with rRNA
    • No functional consequence of MRPL51 loss had been tested
  2. 2010 High

    Demonstrating that MRPL51 directly cross-links to the Oxa1L C-terminal tail on mitochondrial ribosomes established a specific functional interface between MRPL51 and the inner membrane insertase, explaining how the mt-LSU couples translation to membrane protein insertion.

    Evidence Chemical cross-linking of purified Oxa1L-CTT to mitochondrial ribosomes followed by protein identification; binding affinity quantified by isothermal titration calorimetry

    PMID:20601428

    Open questions at the time
    • Atomic-resolution contacts between MRPL51 and Oxa1L-CTT were not resolved
    • Whether MRPL51 is required for Oxa1L function in vivo was untested
  3. 2014 High

    Near-atomic cryo-EM visualization of the human mt-LSU placed MRPL51 within the three-dimensional architecture of the subunit for the first time, enabling structural rationalization of its surface exposure and Oxa1L interaction.

    Evidence Single-particle cryo-EM of the human mt-LSU at 3.4 Å resolution

    PMID:25278503

    Open questions at the time
    • Assembly pathway and order of MRPL51 incorporation remained unknown
    • No mutant or depletion studies in human cells
  4. 2017 High

    Capturing late-stage mt-LSU assembly intermediates by cryo-EM revealed the sequential timing of MRPL51 incorporation relative to rRNA folding, advancing understanding of mitoribosome biogenesis.

    Evidence Cryo-EM of native assembly intermediates from human cells at ~3 Å resolution

    PMID:28892042

    Open questions at the time
    • Assembly factors specifically required for MRPL51 incorporation not identified
    • Whether MRPL51 binding nucleates further assembly events is unknown
  5. 2019 Medium

    Yeast genetic studies uncovered a non-ribosomal role for the MRPL51 ortholog in mtDNA maintenance via interaction with Mhr1, raising the question of whether this dual function is conserved in mammals.

    Evidence Single-gene deletion in yeast; respiratory growth and mtDNA stability assays; co-purification with Mhr1

    PMID:31374566

    Open questions at the time
    • Single-lab study in yeast; conservation in mammalian systems not tested
    • Whether the mtDNA maintenance role is separable from ribosomal function is unresolved
    • Mechanism of Mhr1–Mrpl51 cooperation in mtDNA stability is unclear
  6. 2020 Medium

    A genome-wide CRISPR screen and targeted knockdown showed that MRPL51 loss protects neuroblastoma cells from ischemia-reperfusion-induced apoptosis, linking mitoribosomal function to cell death regulation under metabolic stress.

    Evidence Pooled CRISPR/Cas9 screen under oxygen-glucose deprivation/reperfusion; individual siRNA knockdown with viability and apoptosis readouts

    PMID:32618081

    Open questions at the time
    • Whether the protective effect is specific to MRPL51 or generalizable to mt-LSU depletion is untested
    • Downstream mediators of apoptosis attenuation upon MRPL51 loss not identified
  7. 2020 Medium

    Systematic analysis of MRP expression and knockout phenotypes across mouse development established MRPL51 as individually essential for embryonic viability, with no evidence of functional redundancy among mitoribosomal proteins.

    Evidence Expression profiling of 79 Mrp genes during mouse embryogenesis; compilation of knockout lethality data

    PMID:32987154

    Open questions at the time
    • Specific developmental stage and tissue of lethality for MRPL51 deletion not precisely defined
    • Molecular cause of lethality (e.g., OXPHOS deficit) not directly demonstrated
  8. 2021 Medium

    Quantitative mitochondrial proteomics confirmed MRPL51 mitochondrial localization and established its steady-state abundance and turnover rate, contextualizing it within the broader mitochondrial protein landscape.

    Evidence SILAC-based quantitative mass spectrometry of subcellular fractions

    PMID:34800366

    Open questions at the time
    • Whether MRPL51 turnover is coupled to mitoribosome turnover or independent was not distinguished
  9. 2023 Medium

    Identification of FOXM1 as a direct transcriptional activator of MRPL51 in lung adenocarcinoma, and demonstration that MRPL51 knockdown suppresses EMT and arrests the cell cycle, established a cancer-relevant signaling axis operating through a mitoribosomal gene.

    Evidence ChIP-qPCR and dual-luciferase reporter for FOXM1 binding; siRNA knockdown with EMT marker analysis, invasion assays, and cell cycle profiling in LUAD cells

    PMID:37323822

    Open questions at the time
    • Whether MRPL51's cancer-promoting effects depend on its ribosomal function or a moonlighting activity is unknown
    • In vivo tumor models not employed
    • Generalizability beyond lung adenocarcinoma not assessed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown whether MRPL51 is required for Oxa1L-mediated co-translational insertion in vivo, whether its mtDNA maintenance role in yeast is conserved in mammals, and whether its pro-tumorigenic effects operate through mitoribosomal translation or an independent mechanism.
  • No human cell MRPL51 knockout with OXPHOS functional readouts reported
  • Structural basis of Oxa1L–MRPL51 interaction at residue resolution not available
  • Potential moonlighting functions in mammalian cells not systematically explored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005739 mitochondrion 4
Pathway
GO:0005840 ribosome 3 R-HSA-392499 Metabolism of proteins 3
Partners
MHR1MRPL48MRPL49OXA1L
Complex memberships
mitochondrial large ribosomal subunit (39S)

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MRPL51 was identified as one of 48 distinct protein components of the large (39S) subunit of the mammalian mitochondrial ribosome by proteolytic digestion of whole 39S subunits followed by LC-MS/MS peptide sequencing, establishing it as a bona fide structural constituent of the mt-LSU. Proteolytic digestion of purified 39S subunits, LC-MS/MS peptide sequencing, EST database searching The Journal of biological chemistry High 11551941
2001 MRPL51 was chromosomally mapped to a specific cytogenetic band of the human genome using radiation hybrid panel typing and sequence-tagged sites, revealing that MRP genes including MRPL51 are widely dispersed throughout the genome rather than clustered in operons. Radiation hybrid panel mapping, STS-content mapping Genomics High 11543634
2010 The C-terminal tail of human Oxa1L (Oxa1L-CTT) directly cross-links to MRPL51 (along with MRPL48 and MRPL49) on mammalian mitochondrial ribosomes, indicating MRPL51 is located at or near the ribosomal surface that interacts with the inner membrane insertase Oxa1L during co-translational membrane insertion. Chemical cross-linking of Oxa1L-CTT to mitochondrial ribosomes followed by protein identification; binding stoichiometry and Kd measured by isothermal titration calorimetry The Journal of biological chemistry High 20601428
2014 Cryo-EM structure of the human mitochondrial large ribosomal subunit at 3.4 Å resolution revealed 48 proteins including MRPL51 as a structural component, providing the first near-atomic visualization of MRPL51 within the mt-LSU architecture. Single-particle cryo-electron microscopy at 3.4 Å resolution Science (New York, N.Y.) High 25278503
2017 Cryo-EM structures of two late-stage human mt-LSU assembly intermediates (~3 Å) revealed the sequential incorporation of proteins including MRPL51 during final steps of ribosomal maturation, providing insights into the timing of MRPL51's incorporation relative to rRNA folding. Cryo-EM of native assembly intermediates isolated from human cell lines, ~3 Å resolution Nature structural & molecular biology High 28892042
2019 In yeast, MRPL51 (ortholog of human MRPL51) was found to have a specific role in mitochondrial DNA (mtDNA) stability beyond its structural role in the mitoribosome. Single deletion of MRPL51 caused loss of respiratory growth and loss of mtDNA. The mechanism of mtDNA maintenance by Mrpl51 is likely Mhr1-dependent, as Mhr1 physically interacts with Mrpl51. Yeast reverse genetics (single deletion via alternative approach to avoid double deletion confound), respiratory growth assays, mtDNA stability assays, physical interaction (co-purification with Mhr1) FEMS yeast research Medium 31374566
2020 Genome-wide CRISPR/Cas9 knockout screening in neuroblastoma cells subjected to oxygen-glucose deprivation/reperfusion (OGDR) identified MRPL51 as contributing to OGDR resistance. Individual knockdown of MRPL51 increased cell viability and attenuated OGDR-induced apoptosis, and OGDR treatment itself down-regulated MRPL51 protein expression. Pooled genome-wide CRISPR/Cas9 knockout screen; individual siRNA knockdown; cell viability assays; apoptosis assays; western blotting Journal of cellular and molecular medicine Medium 32618081
2020 Mrpl51 mRNA and protein are upregulated in mouse oocytes following in vitro maturation (IVM) compared to in vivo matured oocytes, but Mrpl51 expression normalizes postnatally in the brain of IVM offspring, suggesting Mrpl51 expression is sensitive to the oocyte maturation environment without lasting developmental consequences. Suppressive subtractive hybridization, RT-PCR, western blot in mouse oocytes and embryos; histological analysis; Morris water maze for cognitive assessment Reproduction (Cambridge, England) Low 21730110
2020 Mrp genes including Mrpl51 are consistently expressed throughout early mouse embryogenesis with little stage or tissue specificity, and are individually essential (most cause early embryonic lethality when deleted), indicating no functional redundancy among MRP family members and that each MRP has a unique, essential role in the mitoribosome. Expression analysis of 79 Mrp genes during mouse development using publicly available datasets; review of existing knockout lethality data Gene expression patterns : GEP Medium 32987154
2023 FOXM1 transcriptionally activates MRPL51 in lung adenocarcinoma by directly binding to the MRPL51 gene promoter. MRPL51 knockdown in LUAD cells suppressed epithelial-mesenchymal transition (decreased N-cadherin and vimentin, increased E-cadherin), induced G1 phase cell cycle arrest, and decreased cell invasion, establishing MRPL51 as a downstream effector of FOXM1 promoting malignant behaviors. Dual-luciferase reporter assay; chromatin immunoprecipitation-qPCR (ChIP-qPCR); siRNA knockdown; western blotting; immunofluorescence; Transwell invasion assay; flow cytometry cell cycle analysis Oncology letters Medium 37323822
2021 MRPL51 was quantified as part of the high-confidence human mitochondrial proteome (MitoCoP) with defined abundance and protein half-life, and confirmed to localize to mitochondria, establishing its steady-state dynamics within the human mitochondrial proteome. Quantitative mass spectrometry of mitochondrial preparations; SILAC-based protein turnover measurements Cell metabolism Medium 34800366
2022 OpenCell endogenous tagging and live-cell imaging confirmed mitochondrial localization of MRPL51, and mass spectrometry-based interaction data placed MRPL51 within the mitoribosomal large subunit protein community. CRISPR-mediated endogenous GFP tagging; confocal live-cell imaging; affinity purification-mass spectrometry Science (New York, N.Y.) Medium 35271311

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
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
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
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 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2014 Structure of the large ribosomal subunit from human mitochondria. Science (New York, N.Y.) 262 25278503
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
2001 The large subunit of the mammalian mitochondrial ribosome. Analysis of the complement of ribosomal proteins present. The Journal of biological chemistry 216 11551941
2000 Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells. Genome research 161 11042152
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2010 A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. The EMBO journal 153 20186120
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2017 Structures of the human mitochondrial ribosome in native states of assembly. Nature structural & molecular biology 136 28892042
2015 Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes. Molecular systems biology 120 25609649
2001 Proteomic analysis of the mammalian mitochondrial ribosome. Identification of protein components in the 28 S small subunit. The Journal of biological chemistry 120 11402041
2022 EZH2 depletion potentiates MYC degradation inhibiting neuroblastoma and small cell carcinoma tumor formation. Nature communications 99 35013218
2020 Systematic mapping of genetic interactions for de novo fatty acid synthesis identifies C12orf49 as a regulator of lipid metabolism. Nature metabolism 92 32694731
2001 The human mitochondrial ribosomal protein genes: mapping of 54 genes to the chromosomes and implications for human disorders. Genomics 88 11543634
2020 Expression analysis of mammalian mitochondrial ribosomal protein genes. Gene expression patterns : GEP 82 32987154
2017 A Single Adaptable Cochaperone-Scaffold Complex Delivers Nascent Iron-Sulfur Clusters to Mammalian Respiratory Chain Complexes I-III. Cell metabolism 78 28380382
2018 RNA-binding proteins with basic-acidic dipeptide (BAD) domains self-assemble and aggregate in Alzheimer's disease. The Journal of biological chemistry 65 29802200
2022 MYC multimers shield stalled replication forks from RNA polymerase. Nature 63 36424410
2018 Systematic Analysis and Biomarker Study for Alzheimer's Disease. Scientific reports 58 30478411
2010 Systems biology of ovine intestinal parasite resistance: disease gene modules and biomarkers. Molecular bioSystems 50 21072409
2022 NUDT21 limits CD19 levels through alternative mRNA polyadenylation in B cell acute lymphoblastic leukemia. Nature immunology 46 36138187
2010 Properties of the C-terminal tail of human mitochondrial inner membrane protein Oxa1L and its interactions with mammalian mitochondrial ribosomes. The Journal of biological chemistry 40 20601428
2010 Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. PloS one 37 20877624
2020 Microarray-based Analysis of Genes, Transcription Factors, and Epigenetic Modifications in Lung Cancer Exposed to Nitric Oxide. Cancer genomics & proteomics 19 32576585
2022 Aberrant mitochondrial homeostasis at the crossroad of musculoskeletal ageing and non-small cell lung cancer. PloS one 9 36067173
2020 CRISPR/Cas9-mediated whole genomic wide knockout screening identifies mitochondrial ribosomal proteins involving in oxygen-glucose deprivation/reperfusion resistance. Journal of cellular and molecular medicine 9 32618081
2011 Altered expression of Armet and Mrlp51 in the oocyte, preimplantation embryo, and brain of mice following oocyte in vitro maturation but postnatal brain development and cognitive function are normal. Reproduction (Cambridge, England) 9 21730110
2023 MRPL51 is a downstream target of FOXM1 in promoting the malignant behaviors of lung adenocarcinoma. Oncology letters 8 37323822
2019 Reverse genetic analysis of yeast YPR099C/MRPL51 reveals a critical role of both overlapping ORFs in respiratory growth and MRPL51 in mitochondrial DNA maintenance. FEMS yeast research 4 31374566
2024 MicroRNAome profiling of breast cancer unveils hsa-miR-5683 as a tumor suppressor microRNA predicting favorable clinical outcome. Cancer cell international 3 39538254