Affinage

MRPL36

Large ribosomal subunit protein bL36m · UniProt Q9P0J6

Length
103 aa
Mass
11.8 kDa
Annotated
2026-06-10
24 papers in source corpus 9 papers cited in narrative 9 extracted findings
Cross-family judge faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MRPL36 (bL36m) is a structural protein of the mitochondrial ribosome large subunit (mtLSU) that is incorporated at a late stage of mtLSU maturation and couples ribosome assembly to mitochondrial protein synthesis (PMID:19339279, PMID:35177605, PMID:40865570). In yeast it associates with the large subunit and stabilizes the interaction between large and small ribosomal subunits; its mitochondria-specific C-terminal domain is dispensable for protein synthesis per se but required for bL36m stability and for assembly of newly made translation products into respiratory chain complexes, with its loss causing rapid degradation of these products (PMID:19339279). Protein stability is governed by a C2-CH zinc finger motif (C66, C69, C82, H88), and disruption of zinc coordination destabilizes the protein and impairs assembly of the L7/L12 stalk base of the large subunit (PMID:38493895). Cryo-EM of assembly intermediates places bL36m incorporation downstream of GTPase- and methyltransferase-dependent rRNA folding events, occurring together with uL6m, uL16m and bL35m after Mtg1 restructures 21S rRNA helices and downstream of GTPBP5 and MRM2 activity (PMID:32652011, PMID:35177605, PMID:40865570). Functionally, yeast bL36m deletion selectively impairs synthesis of mitochondrially encoded cytochrome c oxidase subunits and reduces respiratory growth, whereas in human cells its absence reduces respiration without substantial effects on translation or assembly, indicating species-divergent roles (PMID:41702737). MRPL36 also physically associates with the inner membrane protein LETM1, linking it to regulation of mitochondrial biogenesis and ATP production (PMID:19318571).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2004 Medium

    Established that yeast MrpL36 is an essential large-subunit ribosomal component with separable domains, distinguishing a core translation function from an mRNA-selective activity for COX2.

    Evidence Sucrose gradient sedimentation, deletion/domain-swap genetics, and dosage suppression assays in S. cerevisiae

    PMID:15166137

    Open questions at the time
    • Mechanism of mRNA selection by the N-terminal/Ffh-like domains not defined
    • Did not resolve where in assembly the protein is incorporated
  2. 2009 High

    Defined the functional role of the C-terminal domain in coupling translation to respiratory chain assembly and in stabilizing inter-subunit interactions.

    Evidence Genetic deletion/truncation, pulse-chase, sucrose gradient sedimentation, and respiratory complex assembly assays in yeast

    PMID:19339279

    Open questions at the time
    • Structural basis for inter-subunit stabilization not shown
    • Mechanism linking translation product to degradation unclear
  3. 2009 Medium

    Linked MRPL36 to mitochondrial biogenesis regulation through physical association with the inner membrane protein LETM1.

    Evidence Reciprocal Co-immunoprecipitation and adenoviral overexpression with mitochondrial mass and ATP readouts

    PMID:19318571

    Open questions at the time
    • Functional link rests on overexpression only
    • Interaction not confirmed beyond a single lab
    • Mechanism by which LETM1 binding affects ribosome function unknown
  4. 2017 Medium

    Placed MrpL36 within a defined central-protuberance subcomplex, providing structural context for its position in the mitoribosome.

    Evidence Co-immunoprecipitation/co-purification of a mitoribosomal subcomplex with yeast genetics

    PMID:28931599

    Open questions at the time
    • Single biochemical isolation without structural confirmation
    • Order of subcomplex assembly not addressed
  5. 2020 Medium

    Positioned bL36m incorporation downstream of the assembly GTPase GTPBP5 in human mtLSU biogenesis.

    Evidence TALEN KO cell line, sucrose gradient sedimentation, and mass spectrometry of mtLSU particles

    PMID:32652011

    Open questions at the time
    • Direct interaction with GTPBP5 not shown
    • Whether GTPBP5 acts directly on bL36m loading unresolved
  6. 2022 High

    Resolved bL36m incorporation as a late-stage mtLSU assembly checkpoint coordinated with the MALSU1 anti-association module.

    Evidence Cryo-EM of assembly intermediates from MRM2-KO human cells with transcriptome analysis

    PMID:35177605

    Open questions at the time
    • Trigger for bL36m loading not defined
    • Relationship between rRNA methylation status and bL36m occupancy mechanistically open
  7. 2024 High

    Identified the C2-CH zinc finger as the determinant of bL36m stability and showed stability dictates assembly competence and stalk-base formation.

    Evidence Site-directed mutagenesis of zinc-coordinating residues, MS of large-subunit particles, in vitro zinc-binding assays, and yeast growth assays

    PMID:38493895

    Open questions at the time
    • Structural mechanism by which zinc binding promotes L7/L12 stalk-base assembly not directly visualized
    • In vivo zinc loading dynamics unaddressed
  8. 2025 High

    Ordered bL36m incorporation within the late mtLSU maturation pathway relative to other proteins and Mtg1-mediated rRNA refolding.

    Evidence Cryo-EM of assembly intermediates, in vitro reconstitution, genetic epistasis, and biochemical fractionation in yeast

    PMID:40865570

    Open questions at the time
    • Whether co-incorporated proteins are interdependent not fully dissected
    • Conservation of this exact order in humans not established here
  9. 2026 Medium

    Revealed species divergence: yeast bL36m selectively supports cytochrome c oxidase subunit synthesis, while human bL36m loss affects respiration without major translation/assembly defects.

    Evidence Gene deletion in yeast and human cells, pulse-chase translation assays, respiratory complex activity, and mitoribosome structural analysis

    PMID:41702737

    Open questions at the time
    • Molecular basis for COX-selective effect in yeast unknown
    • Mechanism of reduced human respiration despite intact translation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the LETM1 association and the ribosomal assembly role of MRPL36 are mechanistically connected, and how human bL36m influences respiration without affecting translation, remain unresolved.
  • No structural model of the human MRPL36-LETM1 interaction
  • Downstream effector linking bL36m loss to respiratory decline in human cells not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005840 ribosome 5 GO:0005739 mitochondrion 3
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-8953854 Metabolism of RNA 3
Partners
LETM1MRP7MRPL17MRPL28MRPL35MRPL7
Complex memberships
LETM1-MRPL36 complexmitochondrial ribosome large subunit (mtLSU)mitoribosomal central protuberance subcomplex

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 MRPL36 (mitochondrial ribosomal protein L36) physically associates with LETM1, a mitochondrial inner membrane protein, forming a complex. LETM1 acts as an anchor protein for this interaction. LETM1 overexpression reduces mitochondrial biogenesis and ATP production, and this regulation involves the LETM1-MRPL36 complex. Co-immunoprecipitation; adenovirus-mediated overexpression with functional readouts (mitochondrial mass, ATP production) Cancer research Medium 19318571
2004 Yeast MrpL36p (ortholog of human MRPL36) is an essential mitochondrial ribosomal large-subunit component. Its central L31-homologous domain is sufficient for general mitochondrial translation and co-sediments with the large ribosomal subunit. A novel N-terminal sequence and C-terminal Ffh-like domain are required for dosage suppression of COX2 mRNA translation defects but do not sediment with the large subunit, suggesting a separate mRNA-selection function. Sucrose gradient sedimentation, deletion/domain-swap genetics, dosage suppression assays in S. cerevisiae Genetics Medium 15166137
2009 Yeast Mrpl36 is associated with the mitochondrial ribosome large subunit and its mitochondria-specific C-terminal domain is not required for protein synthesis per se but is required for stability of Mrpl36 and for proper assembly of newly synthesized translation products into respiratory chain complexes; its absence leads to rapid degradation of translation products. Overexpression of Mrpl36 increases efficiency of mitochondrial translation. Mrpl36 stabilizes the interaction between large and small ribosomal subunits. Genetic deletion and domain truncation in yeast, pulse-chase analysis, sucrose gradient sedimentation, functional respiratory chain assembly assays Molecular biology of the cell High 19339279
2017 Yeast MrpL36 (bL31) assembles into a subcomplex with MrpL35 (mL38), MrpL7 (uL5), Mrp7 (bL27), MrpL17 (mL46), and MrpL28 (mL40) within the mitoribosomal central protuberance. Co-immunoprecipitation/co-purification of mitoribosomal subcomplex; yeast genetics Molecular biology of the cell Medium 28931599
2020 In GTPBP5-knockout human mitochondria, the mitoribosome large subunit (mtLSU) lacks bL36m (MRPL36), indicating that GTPBP5 function is required upstream of bL36m incorporation into the mtLSU during biogenesis. TALEN-induced KO cell line, sucrose gradient sedimentation, mass spectrometry of mtLSU particles Nucleic acids research Medium 32652011
2022 In human mitochondria, when MRM2 is absent, the mtLSU shows partial occupancy of bL36m (MRPL36) and the MALSU1:L0R8F8:mtACP anti-association module is bound. Cryo-EM structures at 2.6 Å resolution of these intermediates placed bL36m incorporation at a late-stage assembly checkpoint of the mtLSU. Cryo-EM structural analysis of assembly intermediates from MRM2-knockout cells; genome-wide transcriptome analysis Nature communications High 35177605
2024 In S. cerevisiae, the zinc finger C2-CH motif of bL36m (MRPL36 ortholog) is essential for protein stability and mitoribosome assembly. Mutations in any of the four zinc-coordinating residues (C66, C69, C82, H88) reduce protein stability; C66 and C69 mutations have the most pronounced effect. Protein stability directly correlates with mitoribosome assembly competence and respiratory growth. Absence or mutation of bL36m leads to defective assembly of the L7/L12 stalk base of the large subunit. Site-directed mutagenesis of zinc-coordinating residues, mass spectrometry of large subunit particles, in vitro zinc-binding assay with synthetic proteins, yeast growth assays Biochimica et biophysica acta. Molecular cell research High 38493895
2025 In S. cerevisiae, bL36m (MRPL36 ortholog) incorporation into the mitoribosome large subunit occurs during late mtLSU maturation, downstream of Mrh4-mediated bL33m incorporation, Mtg1-mediated rRNA refolding, and uL16m incorporation. Cryo-EM structures of assembly intermediates show that bL36m is incorporated together with uL6m, uL16m, and bL35m after Mtg1 restructures 21S rRNA helices H73–75 and H93. Cryo-EM of assembly intermediates, in vitro reconstitution, genetic epistasis, biochemical fractionation Biochimica et biophysica acta. Molecular cell research High 40865570
2026 In S. cerevisiae, deletion of bL36m (RTC6/MRPL36 ortholog) selectively impairs synthesis of cytochrome c oxidase subunits encoded in the mitochondrial genome, reducing COX activity and growth on non-fermentable carbon sources, without causing global structural abnormalities of mitoribosomes or reducing their mRNA-binding ability. In contrast, in human cells, absence of bL36m does not substantially impact mitochondrial protein synthesis or ribosome assembly, though mitochondrial respiration is reduced. Gene deletion in yeast and human cells, pulse-chase mitochondrial translation assays, respiratory complex activity measurements, mitoribosome structural analysis Biochemistry. Biokhimiia Medium 41702737

Source papers

Stage 0 corpus · 24 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Association of LETM1 and MRPL36 contributes to the regulation of mitochondrial ATP production and necrotic cell death. Cancer research 66 19318571
1987 Primary structures of and genes for new ribosomal proteins A and B in Escherichia coli. Journal of biochemistry 65 3298224
2006 Promoter prediction in the rhizobia. Microbiology (Reading, England) 63 16735738
2015 Single methylation of 23S rRNA triggers late steps of 50S ribosomal subunit assembly. Proceedings of the National Academy of Sciences of the United States of America 61 26261349
2017 Protein S-Bacillithiolation Functions in Thiol Protection and Redox Regulation of the Glyceraldehyde-3-Phosphate Dehydrogenase Gap in Staphylococcus aureus Under Hypochlorite Stress. Antioxidants & redox signaling 49 27967218
2018 Bacterial ribosome heterogeneity: Changes in ribosomal protein composition during transition into stationary growth phase. Biochimie 47 30359641
2009 Mrpl36 is important for generation of assembly competent proteins during mitochondrial translation. Molecular biology of the cell 42 19339279
2022 A late-stage assembly checkpoint of the human mitochondrial ribosome large subunit. Nature communications 39 35177605
2020 Human GTPBP5 (MTG2) fuels mitoribosome large subunit maturation by facilitating 16S rRNA methylation. Nucleic acids research 37 32652011
2017 MrpL35, a mitospecific component of mitoribosomes, plays a key role in cytochrome c oxidase assembly. Molecular biology of the cell 32 28931599
2021 Epigenome-wide analysis of long-term air pollution exposure and DNA methylation in monocytes: results from the Multi-Ethnic Study of Atherosclerosis. Epigenetics 30 33818294
2005 Disruption of rpmJ encoding ribosomal protein L36 decreases the expression of secY upstream of the spc operon and inhibits protein translocation in Escherichia coli. Bioscience, biotechnology, and biochemistry 21 16116291
2020 YkgM and YkgO maintain translation by replacing their paralogs, zinc-binding ribosomal proteins L31 and L36, with identical activities. Genes to cells : devoted to molecular & cellular mechanisms 19 32559334
2019 Integrated analysis of the critical region 5p15.3-p15.2 associated with cri-du-chat syndrome. Genetics and molecular biology 19 30985858
1989 The secY-rpmJ region of the spc ribosomal protein operon in Escherichia coli: structural alterations affecting secY expression. Molecular & general genetics : MGG 18 2671645
1991 Nucleotide sequence of a Lactococcus lactis gene cluster encoding adenylate kinase, initiation factor 1 and ribosomal proteins. Journal of general microbiology 16 1783905
2004 MrpL36p, a highly diverged L31 ribosomal protein homolog with additional functional domains in Saccharomyces cerevisiae mitochondria. Genetics 12 15166137
2023 Knockout of ribosomal protein RpmJ leads to zinc resistance in Escherichia coli. PloS one 10 36961858
2022 Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population. Frontiers in genetics 9 35910207
1996 Overproduction of mycobacterial ribosomal protein S13 induces catalase/peroxidase activity and hypersensitivity to isoniazid in Mycobacterium smegmatis. Gene 9 8621083
2024 The zinc finger motif in the mitochondrial large ribosomal subunit protein bL36m is essential for optimal yeast mitoribosome assembly and function. Biochimica et biophysica acta. Molecular cell research 1 38493895
2026 Functional Divergence of bL36m Protein in Yeast and Human Mitochondrial Ribosomes. Biochemistry. Biokhimiia 0 41702737
2026 African ancestry and risk variants associated with triple-negative breast cancer susceptibility in African American women. Genome medicine 0 42098873
2025 The late stages of yeast mitoribosome large subunit biogenesis. Biochimica et biophysica acta. Molecular cell research 0 40865570

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