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Showing RPL36 — EL36 is a alias.

RPL36

RPL36 alternative reading frame protein · UniProt C0HME6

Length
148 aa
Mass
15.8 kDa
Annotated
2026-06-10
24 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL36 (eL36) is a zinc-ribbon-domain protein component of the eukaryotic 60S large ribosomal subunit, originally isolated as a ~12 kDa basic protein from rat liver ribosomes (PMID:863909, PMID:8484789). Structural work on the bacterial counterpart established its defining fold: a triple-stranded antiparallel beta-sheet stabilized by a CCCH zinc-binding motif (C-X2-C-X12-C-X4-H) whose conserved basic surface forms an extensive rRNA-interaction interface (PMID:10656825). During subunit biogenesis, eL36 is required for processing of 27SA2, 27SA3, and 27SB pre-rRNAs and acts cooperatively with the neighboring ribosomal proteins eL8 and eL15 to shape domain I of 5.8S/25S rRNA in early pre-60S particles, with its depletion also blocking recruitment of A3- and B-class assembly factors (PMID:25119672, PMID:37865285). Beyond its core ribosomal role, RPL36 promotes cell proliferation and G1/S cell cycle progression, a function controlled at the promoter by STAT1 (PMID:28922548), and its mRNA stability is set by m6A modification read by IGF2BP1 (PMID:38367942). RPL36 contributes to cisplatin resistance (PMID:16394183) and behaves as a haploinsufficient tumor suppressor that accelerates KRAS-driven pancreatic tumorigenesis when lost (PMID:25380065). It also exhibits extra-ribosomal activities, selectively modulating Hsp90α mRNA translation (PMID:28090422) and acting as an RNA-binding protein that sorts miR-4432 into extracellular vesicles (PMID:39700429). Notably, an alternative ORF in the same transcript encodes alt-RPL36, a distinct ER-associated protein that, through phosphoserine-dependent binding to the PI transfer protein TMEM24, restrains plasma-membrane PI(4,5)P2 levels and PI3K-AKT-mTOR signaling (PMID:33479206).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1977 High

    Established RPL36 as a genuine constituent of the eukaryotic large ribosomal subunit rather than a contaminant, defining the physical object all later work concerns.

    Evidence Biochemical purification from rat liver 60S subunits with SDS-PAGE and amino acid composition analysis

    PMID:863909

    Open questions at the time
    • No sequence or structural information at this stage
    • Functional role within the ribosome undefined
  2. 1993 High

    Provided the primary sequence and gene-copy context, anchoring RPL36 to the conserved YL39 ribosomal protein family and enabling molecular study.

    Evidence cDNA sequencing with Southern and Northern blotting in rat

    PMID:8484789

    Open questions at the time
    • No three-dimensional structure
    • rRNA contacts not mapped
  3. 2000 High

    Resolved the fold as a zinc-ribbon with a CCCH zinc-coordination site and a basic rRNA-binding surface, explaining how the protein engages rRNA.

    Evidence Solution NMR structure and EXAFS metal validation of Thermus thermophilus L36

    PMID:10656825

    Open questions at the time
    • Structure from bacterial ortholog, not human protein
    • rRNA interface inferred from electrostatics, not co-structure
  4. 2005 Medium

    Defined the determinants of metal selectivity in the zinc-ribbon, showing the fold strongly favors Zn(II) and that specific residues tune affinity without disrupting topology.

    Evidence Site-directed mutagenesis with UV-vis, CD, and NMR metal-binding assays on the bacterial protein (extends 2001 peptide work)

    PMID:11168885 PMID:15747135

    Open questions at the time
    • In vitro biophysics on bacterial protein/peptide
    • Physiological relevance of metal selectivity in the assembled ribosome untested
  5. 2014 Medium

    Placed RPL36 in the 60S biogenesis pathway by showing it is needed for specific pre-rRNA processing steps and physically links to assembly factor Ebp2 and neighboring r-proteins.

    Evidence Multicopy suppressor screen, primer-extension pre-rRNA analysis, and yeast two-hybrid in S. cerevisiae

    PMID:25119672

    Open questions at the time
    • Interaction order and direct vs. indirect contacts not resolved
    • Yeast ortholog; human pathway not directly tested
  6. 2014 Medium

    Demonstrated a context-specific tumor-suppressor role, with haploinsufficient rpl36 loss accelerating oncogenic KRAS-driven cancer, distinguishing it from a generic ribosomal protein.

    Evidence Zebrafish heterozygous mutant crossed to KRAS(G12V) pancreatic model with survival analysis

    PMID:25380065

    Open questions at the time
    • Mechanism linking reduced RPL36 to tumor acceleration unknown
    • Specificity to KRAS context not generalized
  7. 2016 Medium

    Identified an extra-ribosomal translational specialization, with RPL36 levels selectively modulating Hsp90α mRNA translation and chaperone-inhibitor sensitivity.

    Evidence Polysome profiling and Hsp90 inhibitor sensitivity assays after knockdown in rhabdomyosarcoma cells

    PMID:28090422

    Open questions at the time
    • Mechanism of mRNA selectivity not defined
    • Whether effect requires intact ribosome vs. free RPL36 unclear
  8. 2017 Medium

    Connected RPL36 expression to proliferation control via an upstream STAT1/lncRNA regulatory axis acting at the RPL36 promoter.

    Evidence Co-IP-MS, ChIP/promoter binding, fractionation, and cell-cycle assays in glioma cells

    PMID:28922548

    Open questions at the time
    • Direct vs. indirect STAT1 promoter occupancy not fully separated
    • Downstream proliferation effectors of RPL36 not identified
  9. 2020 Medium

    Confirmed the conserved structural-zinc and late-assembly role through bacterial paralog substitution, showing L36 occupies a single binding site essential for 50S maturation.

    Evidence rpmJ deletion, ykgM/YkgO paralog rescue, ribosome fractionation, and in vitro translation in E. coli

    PMID:32559334

    Open questions at the time
    • Bacterial system; eukaryotic zinc-homeostasis link untested
    • Whether human RPL36 has an analogous paralog switch unknown
  10. 2021 High

    Revealed a dual-coding transcript in which an alternative ORF (alt-RPL36) acts independently of ribosome biogenesis to restrain PI3K-AKT-mTOR signaling via phosphoserine-dependent TMEM24 binding at the ER.

    Evidence Alt-ORF detection, Co-IP, CRISPR knockout, PI(4,5)P2 biosensor imaging, phosphosite mutagenesis, and signaling assays

    PMID:33479206

    Open questions at the time
    • Kinase phosphorylating alt-RPL36 not identified
    • Relationship between canonical RPL36 and alt-RPL36 functions not integrated
  11. 2021 Medium

    Showed RPL36 is required in vivo for tissue homeostasis, with knockdown disrupting spermatogenesis through altered cell death, cell cycle, and JAK/STAT gene expression.

    Evidence Testis-specific RNAi, immunofluorescence, TUNEL, and transcriptome analysis in Drosophila

    PMID:33734578

    Open questions at the time
    • Phenotype may reflect general ribosome insufficiency
    • Direct targets of RPL36 in germline not defined
  12. 2024 Medium

    Defined post-transcriptional control of RPL36 abundance, showing m6A destabilizes its mRNA while the reader IGF2BP1 protects the transcript to sustain proliferation.

    Evidence MeRIP-seq, RNA stability assays, and IGF2BP1 gain-of-function rescue in vitro and in benzene-exposed mice

    PMID:38367942

    Open questions at the time
    • Writer/eraser enzymes setting the m6A mark not identified
    • Whether proliferation effect is ribosomal or extra-ribosomal unresolved
  13. 2025 Medium

    Extended RPL36's RNA-binding repertoire to selective miRNA cargo sorting, loading miR-4432 into extracellular vesicles to influence perivascular cell behavior.

    Evidence miRNA pulldown, RNAi, and functional differentiation/adhesion/proliferation assays in TIE2-mutant endothelial cells

    PMID:39700429

    Open questions at the time
    • RNA-binding determinants of RPL36 for miR-4432 not mapped
    • Generality of EV-sorting function beyond venous malformation context unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RPL36's canonical ribosomal role mechanistically connects to its extra-ribosomal activities (selective translation, EV miRNA sorting, tumor suppression) and to the independently acting alt-RPL36 remains unresolved.
  • No structural model of human RPL36 within the 60S subunit in the corpus
  • Mechanism partitioning free vs. ribosome-bound RPL36 functions undefined
  • Causal link between RPL36 dosage and KRAS-context tumor suppression unexplained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0003723 RNA binding 2 GO:0045182 translation regulator activity 1
Localization
GO:0005840 ribosome 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-392499 Metabolism of proteins 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-1640170 Cell Cycle 1
Partners
EBP2EL15EL8IGF2BP1STAT1TMEM24
Complex memberships
60S large ribosomal subunit

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1977 RPL36 (L36) protein was isolated and purified from the 60S ribosomal large subunit of rat liver ribosomes, establishing it as a bona fide component of the eukaryotic large ribosomal subunit. Molecular weight and amino acid composition were determined. Ion exchange chromatography, gel filtration, SDS-PAGE, amino acid composition analysis The Journal of biological chemistry High 863909
1993 The primary amino acid sequence of rat RPL36 was determined: 104 amino acids (N-terminal Met cleaved post-translationally), MW ~12,128 Da, related to yeast ribosomal protein YL39. The mRNA is ~500 nt and there are 8–11 gene copies in the rat genome. cDNA sequencing, Southern blotting, Northern blotting Biochemical and biophysical research communications High 8484789
2000 The solution NMR structure of ribosomal protein L36 from Thermus thermophilus revealed a zinc-ribbon-like fold: a triple-stranded antiparallel beta-sheet with a zinc-binding site (C-X2-C-X12-C-X4-H motif) coordinating zinc via three cysteines and one histidine (N-delta1). EXAFS confirmed equimolar zinc content. The electrostatic surface and conserved basic residues suggest a large L36-rRNA interaction interface. The fold topology resembles zinc-ribbon domains of transcription factors TFIIB and hTFIIS. Solution NMR structure determination, EXAFS spectroscopy, simulated annealing with NOE/dihedral restraints Journal of molecular biology High 10656825
2001 The CCCH zinc-finger motif (C-X2-C-X12-C-X4-H) of Thermus thermophilus L36 binds metal ions with differential affinities in the order Co(II) > Hg(II) > Zn(II), as measured on a synthetic 26-mer peptide containing this motif. Solid-phase peptide synthesis, circular dichroism, capillary electrophoresis, electrospray ionization mass spectrometry, spectroscopic metal-binding assays The journal of peptide research Medium 11168885
2005 Metal-binding affinities of L36 zinc-ribbon protein are modulated by mutations in the beta-sheet hydrophobic cluster and beta-hairpin turn without changing the overall fold. Specifically: His32→Cys decreases affinity for both Zn(II) and Co(II); Tyr24→Trp increases both affinities; His20→Asn also increases both affinities. The protein normally binds Zn(II) ~2800-fold more tightly than Co(II). UV-vis spectroscopy metal-binding assays, circular dichroism, size-exclusion chromatography, 1D and 2D 1H NMR, site-directed mutagenesis Journal of biological inorganic chemistry Medium 15747135
2006 Functional cloning demonstrated that transfection of RPL36 cDNA conferred 2.5- to 3-fold cisplatin resistance in KB-3-1 cells, identifying RPL36 as a gene directly contributing to cisplatin resistance (confirmed in two independent transfection experiments). Retroviral cDNA library functional cloning, cisplatin selection, clonogenic assays, cDNA transfection Molecular pharmacology Medium 16394183
2014 In Saccharomyces cerevisiae, RPL36A/B (encoding L36a/b) is required for processing of 27SA2, 27SA3, and 27SBL pre-rRNAs during 60S ribosomal subunit biogenesis. RPL36A/B overexpression suppresses ebp2 mutant growth defects. Two-hybrid analysis showed L36a/b physically interacts with the assembly factor Ebp2, as well as ribosomal proteins L34a/b and L8 (which are adjacent to the 3′ end of 5.8S rRNA in mature ribosomes). Genetic suppression analysis (multicopy suppressor screen), synthetic growth enhancement, primer-extension pre-rRNA processing analysis, yeast two-hybrid Current genetics Medium 25119672
2014 In a zebrafish pancreatic cancer model, rpl36 heterozygous loss (haploinsufficiency) accelerated KRAS(G12V)-driven tumor progression and decreased survival in pancreatic acinar cells, establishing rpl36 as a haploinsufficient tumor suppressor in this context. rpl23a did not show this effect, indicating specificity. Zebrafish genetic model (rpl36 hi1807/+ heterozygous mutants crossed with ptf1a:gal4VP16;UAS:GFP-KRAS(G12V) transgenic fish), survival analysis, genetic epistasis Zebrafish Medium 25380065
2016 Ribosomal protein eL36 (RPL36) modulates translation of Hsp90α mRNA. Elevated eL36 (and eL42) levels in rhabdomyosarcoma drive high Hsp90 expression and modulate sensitivity to the Hsp90 inhibitor 17-AAG. Polysome profiling showed Hsp90α mRNA is selectively translated under heat stress conditions where global translation is inhibited. Polysome profiling, RNA interference/knockdown, Hsp90 inhibitor sensitivity assay (17-AAG), rhabdomyosarcoma cell lines Translation (Austin, Tex.) Medium 28090422
2017 In glioma cells, RPL36 promotes cell proliferation and G1/S cell cycle progression. STAT1 was identified by mass spectrometry as a protein that interacts with both lncRNA PLAC2 and the RPL36 promoter, binding at the RPL36 promoter to regulate its expression. Nuclear PLAC2 binds STAT1 and interacts with the RPL36 promoter, while cytoplasmic PLAC2 inhibits STAT1 nuclear translocation, thereby decreasing RPL36 expression and inducing cell cycle arrest. Mass spectrometry (co-immunoprecipitation-MS), cell proliferation assays, cell cycle analysis (flow cytometry), nuclear/cytoplasmic fractionation, ChIP/promoter binding assays, siRNA knockdown Journal of cellular and molecular medicine Medium 28922548
2020 In zinc-deficient E. coli, the zinc-binding ribosomal protein L36 (encoded by rpmJ) is replaced at its ribosomal binding site by the paralog YkgO (expressed from the ykgM operon under Zur repressor control). Copy numbers of L36 and YkgO sum to 1, indicating they share a single binding site. Loss of rpmJ impairs late assembly of the 50S particle, reduces in vitro translation, and causes growth defects; YkgO rescues these functions in zur mutant cells. Genetic deletion (rpmJ null mutants), suppressor mutant isolation (zur mutations), ribosome fractionation, in vitro translation assays, copy number quantitation Genes to cells Medium 32559334
2021 Alt-RPL36, a protein co-encoded with human RPL36 from an alternative ORF in the same transcript, partially localizes to the endoplasmic reticulum and interacts with TMEM24 (a PI transfer protein). Knockout of alt-RPL36 increases plasma membrane PI(4,5)P2 levels, upregulates PI3K-AKT-mTOR signaling, and increases cell size. Alt-RPL36 contains four phosphoserine residues; point mutations abolishing these phosphorylations eliminate TMEM24 interaction and consequently ablate alt-RPL36 effects on PI3K signaling and cell size. Alternative ORF detection, co-immunoprecipitation, knockout (CRISPR), PI(4,5)P2 biosensor imaging, PI3K-AKT-mTOR signaling assays (phospho-Western), cell size measurement, phosphosite mutagenesis Nature communications High 33479206
2021 Knockdown of RpL36 in Drosophila melanogaster testes impairs spermatogenesis: causes smaller testes, reduced germ cells (including germ stem cells), enlarged hub cell clusters, fewer mature sperm, increased apoptosis (TUNEL signal in non-germ cells), and reduced pH3-positive (mitotic) germ cells. Transcriptome analysis of knockdown testes showed altered expression of genes in cell death, cell cycle progression, and JAK/STAT signaling pathway. RNAi knockdown (testis-specific), immunofluorescence (Vasa, pH3), TUNEL assay, fertility assay (egg hatch rate), gene expression analysis Journal of experimental zoology. Part B, Molecular and developmental evolution Medium 33734578
2023 In Saccharomyces cerevisiae, depletion of eL36 not only blocks its own assembly into pre-60S particles but also impairs assembly of neighboring ribosomal proteins eL15 and eL8 into early pre-60S particles, and causes loss of most A3- and B-factors (assembly factors for 27SA3 and 27SB pre-rRNA processing). These results indicate that eL36, together with eL8 and eL15, is prerequisite for shaping domain I of 5.8S/25S rRNA within early pre-60S particles. Conditional depletion (in vivo), pre-rRNA processing analysis, mass spectrometry analysis of pre-60S particle composition, genetic/biochemical epistasis Journal of molecular biology Medium 37865285
2024 m6A modification of RPL36 mRNA reduces its stability and thereby decreases RPL36 expression. The m6A reader IGF2BP1 directly binds RPL36 mRNA to attenuate this destabilization, maintaining RPL36 expression and cell proliferation. In benzene-exposed cells/animals, reduced IGF2BP1 leads to hypomethylation and reduced RPL36 expression, impairing cell proliferation; IGF2BP1 overexpression rescues RPL36 mRNA levels and proliferation. m6A transcriptome-wide sequencing (MeRIP-seq), RNA stability assays, IGF2BP1 overexpression (in vitro and in vivo mouse model), mRNA expression analysis, cell proliferation assays Toxicology Medium 38367942
2025 RPL36 functions as an RNA-binding protein and sorting regulator of microRNA-4432 into extracellular vesicles in TIE2(L914F)-mutant endothelial cells (venous malformation model). RPL36-mediated selective loading of miR-4432 into EVs contributes to inhibition of perivascular cell differentiation, adhesion, and proliferation, identified by miRNA pulldown and RNA interference. RNA sequencing (miRNA profiling of cells and EVs), miRNA pulldown, RNA interference, functional assays (differentiation, adhesion, proliferation of umbilical cord stem cells) The British journal of dermatology Medium 39700429

Source papers

Stage 0 corpus · 24 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 LncRNA PLAC2 down-regulates RPL36 expression and blocks cell cycle progression in glioma through a mechanism involving STAT1. Journal of cellular and molecular medicine 87 28922548
1977 Isolation of eukaryotic ribosomal proteins. Purification and characterization of 60 S ribosomal subunit proteins L3, L6, L7', L8, L10, L15, L17, L18, L19, L23', L25, L27', L28, L29, L31, L32, L34, L35, L36, L36', and L37'. The Journal of biological chemistry 68 863909
2021 Alt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24. Nature communications 47 33479206
2000 The solution structure of ribosomal protein L36 from Thermus thermophilus reveals a zinc-ribbon-like fold. Journal of molecular biology 42 10656825
2009 Aromatase inhibitory, radical scavenging, and antioxidant activities of depsidones and diaryl ethers from the endophytic fungus Corynespora cassiicola L36. Phytochemistry 41 19230943
2006 Identification by functional cloning from a retroviral cDNA library of cDNAs for ribosomal protein L36 and the 10-kDa heat shock protein that confer cisplatin resistance. Molecular pharmacology 30 16394183
1995 Rat intestinal galactoside-binding lectin L-36 functions as a structural protein in the superficial squamous cells of the esophageal epithelium. Cell and tissue research 26 7621528
2014 The tumor suppressor rpl36 restrains KRAS(G12V)-induced pancreatic cancer. Zebrafish 21 25380065
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
2022 Antibacterial Effect of Cell-Free Supernatant from Lactobacillus pentosus L-36 against Staphylococcus aureus from Bovine Mastitis. Molecules (Basel, Switzerland) 19 36364454
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
2014 Roles of Ebp2 and ribosomal protein L36 in ribosome biogenesis in Saccharomyces cerevisiae. Current genetics 16 25119672
2001 The metal binding properties of the CCCH motif of the 50S ribosomal protein L36 from Thermus thermophilus. The journal of peptide research : official journal of the American Peptide Society 15 11168885
2005 Modulation of zinc- and cobalt-binding affinities through changes in the stability of the zinc ribbon protein L36. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 9 15747135
2021 Knockdown of RpL36 in testes impairs spermatogenesis in Drosophila melanogaster. Journal of experimental zoology. Part B, Molecular and developmental evolution 8 33734578
1986 Monoclonal antibodies, L-35 and L-36, define novel T cell activation antigens. Journal of immunology (Baltimore, Md. : 1950) 7 3095423
2024 The m6A reader IGF2BP1 attenuates the stability of RPL36 and cell proliferation to mediate benzene hematotoxicity by recognizing m6A modification. Toxicology 6 38367942
2016 Elevated levels of ribosomal proteins eL36 and eL42 control expression of Hsp90 in rhabdomyosarcoma. Translation (Austin, Tex.) 6 28090422
2025 Ribosomal protein L36-mediated selective loading of microRNA-4432 into extracellular vesicles contributes to perivascular cell dysfunction in venous malformations. The British journal of dermatology 5 39700429
2001 Primary structure and transcription patterns of RPL36, a ribosomal protein-encoding gene of the mycoparasitic fungus, Trichoderma hamatum. Current genetics 5 11409180
1993 The primary structure of rat ribosomal protein L36. Biochemical and biophysical research communications 5 8484789
2023 The Role of Ribosomal Proteins eL15 and eL36 in the Early Steps of Yeast 60S Ribosomal Subunit Assembly. Journal of molecular biology 3 37865285
2026 A novel peptide mR63-77 from Rpl36 protein showing potent antibacterial activities. International journal of antimicrobial agents 0 42218987
2004 Primary structure of dihydrofolate reductase and mitochondrial ribosomal protein L36 genes from the basidiomycete Coprinus cinereus. DNA sequence : the journal of DNA sequencing and mapping 0 15620217

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