Affinage

RPL36A

Large ribosomal subunit protein eL42 · UniProt P83881

Length
106 aa
Mass
12.4 kDa
Annotated
2026-06-10
16 papers in source corpus 12 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL36A (eL42) is a component of the large (60S) ribosomal subunit that contributes directly to peptidyl transferase center function and the translation elongation cycle (PMID:19647033, PMID:30550856). Its conserved GGQ-containing motif (47GFGGQTK53) contacts the CCA end of P-site tRNA (PMID:19647033), and mutations in or adjacent to this minidomain impair poly(Phe) synthesis and peptidyl transferase activity toward puromycin, with a shifted side-chain pKa indicating a catalytic contribution (PMID:30550856). Within the human ribosome, cooperative interactions among residues Q45, Q51, and K53 of the conserved QSGYGGQTK motif are specifically required for dissociation of deacylated tRNA from the E site during elongation, independent of subunit assembly (PMID:37716853), and the protein binds tRNA and 28S rRNA with high affinity while engaging the methylated GGQ motif of the termination factor eRF1 through methyl-group contacts (PMID:28567122). RPL36A is post-translationally modified: its N-terminal methionine is removed (PMID:3396452), and the lysine methyltransferase SET7/9 binds eL42 via its MORN domain and methylates it at Lys53, Lys80, and Lys100, thereby modulating global translation (PMID:31751593). Beyond its core ribosomal role, RPL36A can selectively influence translation of specific mRNAs such as Hsp90α under stress (PMID:28090422) and acts as a proliferative factor in cancer, promoting cell cycling and colony formation (PMID:14752831) and operating upstream of the MAPK/ERK pathway to sustain pERK, c-Myc, and ELK1 expression in colorectal cancer cells (PMID:39489085). The protein localizes to nucleoli through determinants in its N-terminal domain (PMID:14752831).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1988 Medium

    Established the primary structure and conservation of the protein, defining it as a member of the L44e family near the peptidyl transferase center and documenting N-terminal methionine removal as a constitutive modification.

    Evidence cDNA and N-terminal protein sequencing of rat L36a with Southern hybridization for gene copy number

    PMID:3396452

    Open questions at the time
    • No direct demonstration of catalytic role in rat protein
    • Functional consequence of Met removal not tested
  2. 2004 Medium

    Connected the protein to subcellular targeting and to a cellular phenotype, showing nucleolar localization driven by N-terminal determinants and a proliferative role in cancer cells.

    Evidence Ectopic over-expression with localization imaging and domain mapping, plus antisense knockdown with colony formation, proliferation, and cell cycle assays in liver cells

    PMID:14752831

    Open questions at the time
    • Does not distinguish ribosomal from extra-ribosomal mechanism of proliferation
    • No molecular pathway identified at this stage
  3. 2009 Medium

    Placed the protein physically at the tRNA substrate site, showing it contacts the CCA end of P-site tRNA in human 80S ribosomes.

    Evidence Zero-length periodate-oxidized tRNA cross-linking to human 80S ribosomes with competition and MS identification

    PMID:19647033

    Open questions at the time
    • Cross-link reported for the RPL36AL paralog
    • Does not establish catalytic contribution, only proximity
  4. 2016 Medium

    Linked eL42 levels to selective translation, showing it can favor Hsp90α mRNA translation while global translation is suppressed during heat stress.

    Evidence Polysome profiling and eL42 level manipulation in rhabdomyosarcoma cells with 17-AAG sensitivity readout

    PMID:28090422

    Open questions at the time
    • Mechanism of mRNA selectivity unknown
    • Direct binding of eL42 to Hsp90α mRNA not shown
  5. 2017 Medium

    Resolved the molecular basis of eL42 participation in translation termination, mapping methylated Gln-51/Lys-53 contacts to the methylated GGQ of eRF1 and quantifying tRNA and rRNA binding.

    Evidence Surface plasmon resonance binding of recombinant wild-type and mutant eL42 against eRF1, tRNA, and 28S rRNA

    PMID:28567122

    Open questions at the time
    • In vitro binding only; functional termination consequence not measured
    • Methylation state of recombinant protein in assay not fully defined
  6. 2017 Low

    Implicated the protein in CAP-independent translation and stress-induced HSP expression in yeast.

    Evidence Gene deletion and genetic analysis in S. cerevisiae monitoring HSP82/HSC82 and CAP-independent translation under acetic acid and heat stress

    PMID:29158977

    Open questions at the time
    • Genetic observation with limited mechanistic resolution on pathway position
    • Direct role of eL42 versus DOM34 not separated
  7. 2018 High

    Demonstrated that the GGQ minidomain is catalytically required, with genetic complementation failure and a depressed side-chain pKa pointing to direct involvement in peptidyl transfer.

    Evidence Site-directed mutagenesis, genetic complementation, poly(Phe) and puromycin assays, and pKa measurement in S. pombe

    PMID:30550856

    Open questions at the time
    • Catalytic mechanism in human ribosome inferred from yeast ortholog
    • No high-resolution structure of the catalytic geometry
  8. 2019 High

    Identified SET7/9 as a methyltransferase for eL42 and tied this modification to control of global translation.

    Evidence Yeast two-hybrid, co-IP, GST pulldown, methylation-site mutagenesis, and puromycin incorporation assay

    PMID:31751593

    Open questions at the time
    • Quantitative stoichiometry of methylation in vivo unknown
    • How methylation alters ribosome behavior mechanistically not resolved
  9. 2021 Medium

    Connected RPL36A to the DNA damage and apoptotic response, showing knockdown increases radiosensitivity in oral squamous cell carcinoma.

    Evidence siRNA knockdown with irradiation, DNA damage markers, cell cycle flow cytometry, and apoptosis assays in OSCC lines

    PMID:34830778

    Open questions at the time
    • Whether the effect is via translation or an extra-ribosomal route is unresolved
    • No direct molecular target of the radiosensitization identified
  10. 2022 Medium

    Proposed eL42 incorporation level as a source of ribosome heterogeneity, with paralog deletion phenotypes tracing to Rpl42p abundance rather than sequence.

    Evidence Paralog gene deletion, polysome profiling, Western blotting of translating fractions, and epistasis in S. pombe

    PMID:35954225

    Open questions at the time
    • Functional consequence of heterogeneous eL42 content on specific mRNAs unknown
    • Relevance to human ribosomes untested
  11. 2023 High

    Defined a specific elongation step for eL42 in human ribosomes, showing cooperative Q45/Q51/K53 interactions are required for deacylated tRNA release from the E site without affecting subunit assembly.

    Evidence Conserved-motif mutagenesis in FLAG-tagged eL42 in HEK293T cells with polysome profiling, tRNA binding, and peptidyl transferase assays

    PMID:37716853

    Open questions at the time
    • Structural basis of the E-site coupling not visualized
    • Interplay with methylation state of these residues not tested
  12. 2024 Medium

    Placed RPL36A upstream of MAPK/ERK signaling in cancer, with knockdown reducing pERK/c-Myc/ELK1 and ERK activation rescuing the phenotype.

    Evidence siRNA knockdown in CRC lines with Western blotting, ERK-activator rescue, and xenograft growth assay

    PMID:39489085

    Open questions at the time
    • Direct molecular link between RPL36A and ERK activation not defined
    • Whether the effect requires ribosomal function is unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the catalytic, termination, methylation, mRNA-selectivity, and extra-ribosomal signaling functions are integrated, and the structural basis of eL42's E-site role, remain unresolved.
  • No high-resolution structure of eL42 in the catalytically engaged ribosome
  • Mechanism coupling ribosomal residence to MAPK/ERK activation undefined
  • Physiological role of methylation-dependent eRF1 interaction in cells not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0005198 structural molecule activity 2 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005840 ribosome 2 GO:0005730 nucleolus 1
Pathway
R-HSA-162582 Signal Transduction 1
Partners
ERF1SETD7
Complex memberships
60S ribosomal subunit

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 Over-expressed L36a/RPL36A ribosomal protein localizes to the nucleoli of cells, and this localization is controlled by the N-terminal or the internal tetrapeptide consensus sequence with its adjacent N-terminal domain. Ectopic over-expression with subcellular localization imaging (nucleolar localization assay); N-terminal domain mapping Hepatology Medium 14752831
2004 Over-expression of RPL36A leads to enhanced colony formation and cell proliferation via accelerated cell cycling; antisense cDNA effectively reversed these effects, establishing a direct role for RPL36A in promoting cellular proliferation. Ectopic over-expression and antisense knockdown with colony formation assay, proliferation assay, and cell cycle analysis Hepatology Medium 14752831
2009 The large subunit ribosomal protein RPL36A-like (RPL36AL/eL42) contacts the CCA end of P-site bound tRNA in human 80S ribosomes, placing it at or near the binding site for the tRNA substrate of the peptidyl transferase reaction. Periodate-oxidized tRNA (zero-length affinity labeling reagent) cross-linking to human 80S ribosomes, with competition by intact tRNA and protein identification by mass spectrometry Biochimie Medium 19647033
1988 Rat ribosomal protein L36a (homolog of human RPL36A) contains 105 amino acids (N-terminal Met removed post-translationally) and is homologous to human HL44 and yeast protein 44, suggesting conservation of the L44e family at the peptidyl transferase center. cDNA sequencing of recombinant clone, N-terminal amino acid sequencing, Southern hybridization for gene copy number DNA (Mary Ann Liebert, Inc.) Medium 3396452
2017 The monomethylated Gln-51 and Lys-53 residues within the 47GFGGQTK53 motif of human eL42 (RPL36A) mediate interaction with the methylated GGQ motif of eRF1 via hydrophobic contacts between methyl groups; eL42 also interacts with tRNA (nanomolar KD) and 28S rRNA (picomolar KD) through strong binding affinities. Biacore surface plasmon resonance binding assay using recombinant wild-type and mutant eL42 proteins (GGQTK deletion, Q51E, K53Q, Q51A/K53A double mutant) against eRF1, tRNA, and 28S rRNA The open biochemistry journal Medium 28567122
2018 The GGQ minidomain and neighboring region of eL42 (RPL36A ortholog) is critical for ribosomal function in S. pombe; mutations within or adjacent to the GGQ minidomain fail to complement wild-type eL42 and cause growth defects, reduced poly(Phe) synthesis, and reduced peptidyl transferase activity toward puromycin. A pKa of 6.95 was measured for the side chain of Lys-55/Arg-55, substantially less than a free Lys or Arg, indicating involvement in catalysis. Site-directed mutagenesis, genetic complementation in S. pombe, in vitro poly(Phe) synthesis assay, peptidyl transferase (puromycin) assay, pKa measurement Biochimie High 30550856
2019 The lysine methyltransferase SET7/9 interacts with eL42 (RPL36A) via its N-terminal MORN domain, and methylates eL42 at three lysines (Lys53, Lys80, Lys100); SET7/9-mediated methylation of eL42 affects global protein translation. Yeast two-hybrid screening, co-immunoprecipitation, GST pulldown, site-directed mutagenesis of methylation sites, puromycin incorporation assay for translation Biochimica et biophysica acta. Molecular cell research High 31751593
2016 Elevated levels of eL42 (RPL36A) modulate Hsp90α expression under both normal and heat shock conditions in rhabdomyosarcoma cells; polysome profiling showed selective translation of Hsp90α mRNA while global translation is inhibited during heat stress. Polysome profiling, manipulation of eL42 levels in rhabdomyosarcoma cells with measurement of Hsp90α expression and sensitivity to Hsp90 inhibitor 17-AAG Translation (Austin, Tex.) Medium 28090422
2017 RPL36A and DOM34 influence CAP-independent translation in yeast and affect expression of HSP82 and HSC82 heat shock proteins in response to acetic acid stress. Gene deletion/genetic analysis in S. cerevisiae, monitoring of HSP protein expression and CAP-independent translation under acetic acid and heat stress PeerJ Low 29158977
2021 Knockdown of RPL36A in oral squamous cell carcinoma cells increased radiosensitivity by sensitizing cells to DNA damage, promoting G2/M cell cycle arrest, and augmenting irradiation-induced apoptosis. siRNA knockdown of RPL36A in OSCC cell lines, irradiation, measurement of DNA damage markers, cell cycle analysis by flow cytometry, apoptosis assay Cancers Medium 34830778
2023 Cooperative interactions involving eL42 (RPL36A) residues Q45, Q51, and K53 within the conserved QSGYGGQTK motif are critical for the human ribosome elongation cycle specifically at the step of deacylated tRNA dissociation from the E site; double substitutions at positions 45+51 or 45+53 decrease polysomes without affecting 60S or 80S assembly. Site-directed mutagenesis of conserved motif residues in FLAG-tagged eL42, expression in HEK293T cells, polysome profiling with Western blotting, tRNA binding assay, peptidyl transferase activity assay Biochimie High 37716853
2024 RPL36A depletion in colorectal cancer cells diminishes phosphorylated ERK levels and subsequently reduces expression of c-Myc and ELK1; the tumor-suppressive effects of RPL36A knockdown are negated by an ERK activator, placing RPL36A upstream of the MAPK/ERK pathway. siRNA knockdown of RPL36A in CRC cell lines, Western blotting for pERK/c-Myc/ELK1, rescue with ERK activator, tumor xenograft growth assay Translational oncology Medium 39489085
2022 In S. pombe, the level of Rpl42p (eL42/RPL36A ortholog) in actively translating ribosomes varies depending on which 40S ribosomal protein paralog is present, identifying variation in eL42 incorporation as a potential form of ribosome heterogeneity; phenotypic differences of rps8 paralog deletions reside in Rpl42p level variation rather than in protein sequence differences between the Rps8 paralogs. Genetic deletion of paralog genes in fission yeast, polysome profiling, Western blotting to quantify Rpl42p in translating fractions, epistasis analysis Cells Medium 35954225

Source papers

Stage 0 corpus · 16 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Over-expression of the ribosomal protein L36a gene is associated with cellular proliferation in hepatocellular carcinoma. Hepatology (Baltimore, Md.) 88 14752831
2014 Abiotic stress resistance, a novel moonlighting function of ribosomal protein RPL44 in the halophilic fungus Aspergillus glaucus. Applied and environmental microbiology 41 24814782
2009 The human large subunit ribosomal protein L36A-like contacts the CCA end of P-site bound tRNA. Biochimie 25 19647033
2019 SET7/9 interacts and methylates the ribosomal protein, eL42 and regulates protein synthesis. Biochimica et biophysica acta. Molecular cell research 14 31751593
2017 The sensitivity of the yeast, Saccharomyces cerevisiae, to acetic acid is influenced by DOM34 and RPL36A. PeerJ 14 29158977
2021 Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma. Cancers 12 34830778
1988 Primary structure of rat ribosomal protein L36a. DNA (Mary Ann Liebert, Inc.) 11 3396452
2016 Elevated levels of ribosomal proteins eL36 and eL42 control expression of Hsp90 in rhabdomyosarcoma. Translation (Austin, Tex.) 6 28090422
2022 Differential Paralog-Specific Expression of Multiple Small Subunit Proteins Cause Variations in Rpl42/eL42 Incorporation in Ribosome in Fission Yeast. Cells 5 35954225
2018 Ribosomal protein eL42 contributes to the catalytic activity of the yeast ribosome at the elongation step of translation. Biochimie 5 30550856
2024 RPL36A activates ERK pathway and promotes colorectal cancer growth. Translational oncology 3 39489085
2010 [Proliferation promotion and apoptotic inhibition effects of ribosomal protein RPL36A small interference RNA on U937 cells]. Zhongguo shi yan xue ye xue za zhi 3 20416165
2017 A Functional Role for the Monomethylated Gln-51 and Lys-53 Residues of the 49GGQTK53 Motif of eL42 from Human 80S Ribosomes. The open biochemistry journal 2 28567122
2023 Functional involvement of a conserved motif in the middle region of the human ribosomal protein eL42 in translation. Biochimie 1 37716853
2000 Molecular cloning and complete cDNA sequences of the ribosomal proteins rpl34 and rpl44 from Aedes triseriatus mosquitoes. DNA sequence : the journal of DNA sequencing and mapping 1 11328654
1994 RPL44 and RPL44', encoding acidic ribosomal phosphoproteins YP2 alpha(L44) and YP1 beta(L44'), are adjacent to rig and STF1 on Saccharomyces cerevisiae chromosomes XV and IV respectively. Yeast (Chichester, England) 0 7941754

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