Affinage

MRPL23

Large ribosomal subunit protein uL23m · UniProt Q16540

Round 2 corrected
Length
153 aa
Mass
17.8 kDa
Annotated
2026-04-28
54 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MRPL23 (uL23m) is a structural protein of the mammalian mitochondrial large ribosomal subunit (39S/mt-LSU), essential for mitochondrial translation of the 13 oxidative phosphorylation subunits encoded by mitochondrial DNA. Cryo-EM structures at near-atomic resolution place MRPL23 within the 48-protein mt-LSU architecture, including in late-stage assembly intermediates that reveal its incorporation during ribosomal maturation (PMID:25278503, PMID:28892042). Genetic disruption of the yeast ortholog causes respiratory deficiency or lethality depending on species, and mouse knockout results in early embryonic lethality, demonstrating a non-redundant requirement for mitochondrial protein synthesis (PMID:10743564, PMID:32987154). The MRPL23 locus on human 11p15.5 is biallelically expressed and insulated from the adjacent IGF2/H19 imprinted domain by a conserved CTCF-dependent boundary element (PMID:12075007, PMID:8541832).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1995 Medium

    Cloning of MRPL23 established it as a nuclear-encoded mitochondrial ribosomal protein gene located immediately downstream of the H19 imprinted locus, raising the question of how it escapes imprinting control.

    Evidence cDNA cloning, Northern blot, and allele-specific expression analysis in human fetal and adult tissues

    PMID:8541832

    Open questions at the time
    • No functional data on its ribosomal role in mammalian cells
    • Mechanism of insulation from imprinted domain unknown
  2. 1997 High

    Targeted enhancer deletion in mouse demonstrated that MRPL23 is functionally insulated from the upstream Igf2/H19 enhancers and imprinting machinery, ruling out shared regulatory control.

    Evidence Mouse targeted enhancer deletion, allele-specific expression, CpG island promoter characterization

    PMID:9344651

    Open questions at the time
    • Molecular identity of the insulator element not yet defined
    • Whether insulation is chromatin-mediated or sequence-mediated was unresolved
  3. 2000 High

    Cross-species complementation showed that MRPL23 is a bona fide essential component of the mitochondrial ribosome large subunit required for mitochondrial translation, answering whether it has a direct functional role in mitoribosome activity.

    Evidence Gene disruption in K. lactis (lethal) and S. cerevisiae (respiratory deficiency), cross-species complementation

    PMID:10743564

    Open questions at the time
    • No structural data on where MRPL23 resides within the mt-LSU
    • Mammalian loss-of-function phenotype not yet characterized
  4. 2002 High

    Identification of a conserved CTCF-binding insulator element between H19 and MRPL23 resolved the mechanism by which this locus is shielded from the adjacent imprinted domain, establishing CTCF as the boundary factor.

    Evidence CTCF ChIP, DNase I hypersensitivity mapping, transfection-based insulator reporter assay, human-mouse conservation analysis

    PMID:12075007 PMID:12589428 PMID:9618174

    Open questions at the time
    • Whether deletion of this CTCF site in vivo would cause MRPL23 to become imprinted was not tested
    • Relationship between CTCF boundary and Beckwith-Wiedemann syndrome pathogenesis at this locus not determined
  5. 2014 High

    Near-atomic cryo-EM of the human mt-LSU resolved MRPL23 as one of 48 structural proteins and revealed the remodeled exit tunnel and central protuberance architecture, placing it in a definitive structural context.

    Evidence Single-particle cryo-EM of the human 39S subunit at 3.4 Å resolution

    PMID:25278503

    Open questions at the time
    • Specific contacts of MRPL23 with rRNA and neighboring proteins not individually characterized
    • No structure of the complete 55S translating ribosome at this resolution
  6. 2017 High

    Cryo-EM of late assembly intermediates revealed the timing and pathway of mt-LSU maturation, establishing when MRPL23 is incorporated during subunit biogenesis.

    Evidence Cryo-EM at ~3 Å of native mt-LSU assembly intermediates

    PMID:28892042

    Open questions at the time
    • Order of MRPL23 incorporation relative to other MRPs not individually resolved
    • Assembly chaperones specific to MRPL23 not identified
  7. 2020 Medium

    Systematic expression and knockout analyses across all 79 mouse MRP genes showed MRPL23 is ubiquitously expressed in development and non-redundant, as its loss causes early embryonic lethality.

    Evidence In situ hybridization and RT-PCR across developmental stages; analysis of lethal knockout phenotypes

    PMID:32987154

    Open questions at the time
    • Precise embryonic stage and mechanism of lethality not characterized
    • Whether lethality reflects global mitochondrial translation failure or specific substrate loss is unknown
  8. 2020 Medium

    Proteomic and proximity-labeling studies confirmed MRPL23 as a stable mitochondrial resident with defined abundance and turnover, and mapped its interaction neighborhood within the mt-LSU.

    Evidence Quantitative mass spectrometry (MitoCoP), BioID proximity labeling with mitochondrial baits

    PMID:27499296 PMID:32877691 PMID:34800366

    Open questions at the time
    • No direct interactor list for MRPL23 specifically (systemic study)
    • Turnover regulation mechanisms unknown
  9. 2025 Medium

    MRPL23 knockdown in hepatocellular carcinoma cells triggered HMGB1-dependent cellular senescence and suppressed tumor growth in xenografts, revealing an unexpected extra-ribosomal axis linking MRPL23 to senescence regulation.

    Evidence siRNA/shRNA knockdown, senescence assays, HMGB1 pharmacological inhibition (NecroX-7), mouse xenograft model

    PMID:40490666

    Open questions at the time
    • Whether the senescence effect is mediated by mitochondrial translation deficiency or a direct MRPL23–HMGB1 interaction is unresolved
    • Single-lab finding without independent replication
    • Mechanism linking MRPL23 to HMGB1 regulation not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown whether the HMGB1-dependent senescence phenotype upon MRPL23 loss reflects a moonlighting function or a downstream consequence of mitochondrial translation failure, and no direct protein-protein interaction between MRPL23 and HMGB1 has been demonstrated.
  • No reconstituted biochemical activity for MRPL23 outside the ribosome
  • No patient mutations in MRPL23 linked to mitochondrial disease
  • Structural basis for MRPL23's specific contributions to mt-LSU function versus other MRPs is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 4
Localization
GO:0005739 mitochondrion 6 GO:0005840 ribosome 4
Pathway
R-HSA-392499 Metabolism of proteins 4
Complex memberships
mitochondrial ribosome large subunit (39S/mt-LSU)

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 MRPL23 (originally named L23MRP) was identified as a novel gene located ~40 kb downstream of the imprinted H19 gene on chromosome 11p15.5, encoding a mitochondrial ribosomal large subunit protein. It is biallelically expressed in mid-fetal and adult human tissues, indicating it is functionally insulated from the IGF2/H19 imprinted domain. cDNA cloning, Northern blot, allele-specific expression analysis Human molecular genetics Medium 8541832
1997 The mouse ortholog L23mrp maps to the conserved syntenic region on distal chromosome 7. Its promoter is a CpG island driving ubiquitous transcription. Both parental alleles are equally active (biallelic expression). Targeted deletion of enhancers shared by Ins-2/Igf-2/H19 does not affect L23mrp expression, demonstrating that L23mrp is functionally insulated from the upstream imprinted domain in terms of both imprinting and enhancer action. Mouse gene cloning, allele-specific expression analysis, targeted enhancer deletion mouse model Genomics High 9344651
1998 The murine imprinting cluster on distal chromosome 7 (~1 Mb) is demarcated at its 3' end by L23mrp (Rpl23l/MRPL23), which is directly flanked by and non-imprinted, establishing MRPL23 as a boundary marker of the Beckwith-Wiedemann syndrome imprinted domain. Physical contig mapping, FISH, expression analysis across tissues Human molecular genetics Medium 9618174
2000 In Kluyveromyces lactis, disruption of MRP-L23 (encoding a mitochondrial large subunit ribosomal protein with 43% identity to E. coli L13) is lethal, whereas in Saccharomyces cerevisiae it only causes respiratory deficiency. The K. lactis protein can complement the respiratory-deficient phenotype of S. cerevisiae mrp-L23 mutants, demonstrating that MRPL23 is an essential component of the mitochondrial ribosome large subunit required for mitochondrial protein synthesis. Gene disruption, complementation assay, growth on non-fermentable carbon sources Current genetics High 10743564
2002 MRPL23 and flanking genes (2G7, TNNT3) in the 100 kb immediately downstream of H19 are biallelically expressed, confirming that H19 marks one border of the imprinted domain and that MRPL23 resides outside the imprinted region. Allele-specific expression analysis in multiple fetal and adult tissues (human and mouse) Human genetics Medium 12589428
2002 A CTCF binding site in the intergenic region between H19 and L23mrp acts as an insulator element at the 3' boundary of the imprinted Igf2/H19 domain. This site is conserved between human and mouse, associated with a DNase I-hypersensitive site, bound by CTCF in vivo, and functions as an insulator in reporter assays. This element contributes to the functional insulation of MRPL23 from the upstream imprinted domain. CTCF binding site identification, DNase I hypersensitivity, chromatin immunoprecipitation (in vivo CTCF binding), transfection-based reporter insulator assay Human molecular genetics High 12075007
2002 Mammalian mitochondrial ribosomes (55S) have evolved a protein-rich composition with up to 80 MRPs (including MRPL23) that have replaced RNA structural elements found in bacterial ribosomes. MRPL23 is encoded by a nuclear gene, imported into mitochondria, and assembled with mitochondrially transcribed rRNAs to form the large subunit responsible for translating the 13 mRNAs encoding essential oxidative phosphorylation proteins. Biochemical characterization of bovine mitoribosomal proteins, amino acid sequencing, evolutionary analysis Gene Medium 11943462
2014 Cryo-EM structure of the human mitochondrial large ribosomal subunit at 3.4 Å resolution revealed 48 proteins including MRPL23 as a structural component. The structure showed adaptations of the exit tunnel for hydrophobic nascent peptides and extensive remodeling of the central protuberance, placing MRPL23 in the context of the 39S large subunit architecture. Single-particle cryo-electron microscopy at 3.4 Å resolution Science High 25278503
2016 MRPL23 is confirmed as a protein component of the human mitochondrial ribosome large subunit (mt-LSU) through mitochondrial protein interaction mapping using affinity enrichment mass spectrometry. Its interactions are consistent with a structural role in the large subunit. Affinity enrichment mass spectrometry (mitochondrial protein interaction mapping) Molecular cell Medium 27499296
2017 Cryo-EM structures of two late-stage assembly intermediates of the human mitoribosomal large subunit (~3 Å resolution) revealed details of rRNA folding and protein incorporation timing during ribosomal maturation, placing MRPL23 within the assembly pathway of the mt-LSU. The structures identified assembly factors including RsfS, L0R8F8, and mt-ACP. Single-particle cryo-EM at ~3 Å resolution of native assembly intermediates Nature structural & molecular biology High 28892042
2018 MRPL23 is located within the IGF2 locus alongside Th and other conserved genes across vertebrates including fish, confirming that MRPL23 (Mrpl23) has been a stable component of the Igf2 chromosomal locus since early vertebrate ancestors, consistent with its conserved role as a mitochondrial ribosomal protein. Comparative genomics using genome and gene expression repositories across >20 vertebrate species The Journal of biological chemistry Low 30154247
2020 MRPL23 is identified as an essential component of the mitoribosome complex in mammals. Expression profiling across 79 Mrp genes during mouse development shows consistent expression throughout early embryogenesis with little stage or tissue specificity, and genetic evidence indicates that Mrpl23 loss results in early embryonic lethality, demonstrating no functional redundancy among MRP family members. mRNA expression profiling (in situ hybridization and RT-PCR across developmental stages), analysis of lethal knockout phenotypes Gene expression patterns : GEP Medium 32987154
2020 MRPL23 is identified as a component of the high-confidence human mitochondrial proteome (MitoCoP) with defined abundance and half-life dynamics, confirming its residence in the mitochondrial compartment in cellular context. Quantitative mass spectrometry of mitochondrial preparations combined with protein turnover measurements Cell metabolism Medium 34800366
2020 BioID proximity interaction mapping of mitochondrial proteins confirmed MRPL23's proximity interactions within the mitochondrial large subunit environment, consistent with its structural role in the mt-LSU. BioID proximity-dependent biotinylation with 100 mitochondrial baits, mass spectrometry Cell metabolism Medium 32877691
2024 Single-cell transcriptome analysis combined with lentiviral barcoding (SCALeBa) in human HSPCs revealed that cells expressing high levels of MRPL23 show a differentiation bias toward the myeloid lineage in vivo, suggesting MRPL23 expression is associated with myeloid fate determination in hematopoietic progenitors. Single-cell RNA-seq with lentiviral barcoding for clonal tracking in vivo, validated in independent dataset Clinical and translational medicine Low 39538416
2025 Suppression of MRPL23 in hepatocellular carcinoma cells decreases cell proliferation and promotes cellular senescence. MRPL23 regulates senescence by targeting HMGB1, as demonstrated using the HMGB1 inhibitor NecroX-7. MRPL23 deficiency also protects against HCC progression in a mouse model, identifying MRPL23 as an oncogenic factor whose loss triggers a senescence barrier to tumor growth. siRNA/shRNA knockdown, cell proliferation assay, senescence assays, mouse xenograft model, pharmacological inhibition with NecroX-7 Discover oncology Medium 40490666

Source papers

Stage 0 corpus · 54 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
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
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
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
2008 Genome-scale RNAi screen for host factors required for HIV replication. Cell host & microbe 627 18976975
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
2004 Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation. Nature biotechnology 266 15146197
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 Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function. Molecular cell 220 27499296
2016 Structure and Function of the Mitochondrial Ribosome. Annual review of biochemistry 217 27023846
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
2007 5-fluorouracil activation of p53 involves an MDM2-ribosomal protein interaction. The Journal of biological chemistry 167 17242401
2010 A functional peptidyl-tRNA hydrolase, ICT1, has been recruited into the human mitochondrial ribosome. The EMBO journal 153 20186120
2015 BioID-based Identification of Skp Cullin F-box (SCF)β-TrCP1/2 E3 Ligase Substrates. Molecular & cellular proteomics : MCP 149 25900982
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
2002 Evolution of a protein-rich mitochondrial ribosome: implications for human genetic disease. Gene 105 11943462
1998 Syntenic organization of the mouse distal chromosome 7 imprinting cluster and the Beckwith-Wiedemann syndrome region in chromosome 11p15.5. Human molecular genetics 102 9618174
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2020 Expression analysis of mammalian mitochondrial ribosomal protein genes. Gene expression patterns : GEP 82 32987154
2020 Long Noncoding RNA MRPL23-AS1 Promotes Adenoid Cystic Carcinoma Lung Metastasis. Cancer research 64 32098781
2021 Long non-coding RNA (LncRNA) MRPL23-AS1 promotes tumor progression and carcinogenesis in osteosarcoma by activating Wnt/β-catenin signaling via inhibiting microRNA miR-30b and upregulating myosin heavy chain 9 (MYH9). Bioengineered 51 33356805
1997 A 1-Mb physical map and PAC contig of the imprinted domain in 11p15.5 that contains TAPA1 and the BWSCR1/WT2 region. Genomics 51 9268640
1995 A novel L23-related gene 40 kb downstream of the imprinted H19 gene is biallelically expressed in mid-fetal and adult human tissues. Human molecular genetics 47 8541832
2009 To bleed or not to bleed. A prediction based on individual gene profiling combined with dose-volume histogram shapes in prostate cancer patients undergoing three-dimensional conformal radiation therapy. International journal of radiation oncology, biology, physics 42 19211196
2021 Comprehensive analysis of lncRNA-miRNA-mRNA regulatory networks for microbiota-mediated colorectal cancer associated with immune cell infiltration. Bioengineered 27 34227920
2018 Genetic variants in lncRNA H19 are associated with the risk of oral squamous cell carcinoma in a Chinese population. Oncotarget 26 29844862
2002 An evolutionarily conserved putative insulator element near the 3' boundary of the imprinted Igf2/H19 domain. Human molecular genetics 26 12075007
2022 Identification of Immune Cells and Key Genes associated with Alzheimer's Disease. International journal of medical sciences 23 34975305
2020 Risk Scoring System based on lncRNA Expression for Predicting Survival in Hepatocellular Carcinoma with Cirrhosis. Asian Pacific journal of cancer prevention : APJCP 19 32592379
2018 The insulin-like growth factor 2 gene and locus in nonmammalian vertebrates: Organizational simplicity with duplication but limited divergence in fish. The Journal of biological chemistry 18 30154247
1997 Structure and expression of the mouse L23mrp gene downstream of the imprinted H19 gene: biallelic expression and lack of interaction with the H19 enhancers. Genomics 16 9344651
2020 Association between lncRNA-H19 polymorphisms and hepatoblastoma risk in an ethic Chinese population. Journal of cellular and molecular medicine 15 33236528
2022 Long non-coding RNA MRPL23-AS1 suppresses anoikis in salivary adenoid cystic carcinoma in vitro. Oral diseases 11 35175670
2003 Biallelic expression of HRAS and MUCDHL in human and mouse. Human genetics 8 12589428
2017 Genetic Analysis of Mitochondrial Ribosomal Proteins and Cognitive Aging in Postmenopausal Women. Frontiers in genetics 7 28983317
2000 Disruption of the MRP-L23 gene encoding the mitochondrial ribosomal protein L23 is lethal for Kluyveromyces lactis but not for Saccharomyces cerevisiae. Current genetics 6 10743564
2025 Integrative bioinformatics approach identifies novel drug targets for hyperaldosteronism, with a focus on SHMT1 as a promising therapeutic candidate. Scientific reports 4 39799159
2024 LncRNA microarray profiling identifies novel circulating lncRNAs in hidradenitis suppurativa. Molecular medicine reports 3 38757342
2025 Suppression of MRPL23 induces cellular senescence in hepatocellular carcinoma by targeting HMGB1. Discover oncology 2 40490666
2025 Comprehensive genome-wide analysis of retinal vessel caliber reveals microvascular-blood pressure pathways: advancing predictive, preventive, and personalized medicine. The EPMA journal 1 40438498
2024 Molecular characterization of human HSPCs with different cell fates in vivo using single-cell transcriptome analysis and lentiviral barcoding technology. Clinical and translational medicine 0 39538416