Affinage

RPL37A

Large ribosomal subunit protein eL43 · UniProt P61513

Round 2 corrected
Length
92 aa
Mass
10.3 kDa
Annotated
2026-04-28
43 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL37A (eL43) is a core structural component of the 60S large ribosomal subunit that participates in cytoplasmic translation. The protein is a small (~91–92 amino acid) polypeptide harboring a conserved C2-C2 zinc finger motif implicated in ribosomal RNA contacts, and its position within the 60S subunit has been resolved at near-atomic resolution by cryo-EM of the human 80S ribosome (PMID:23636399, PMID:25901680). The RPL37A gene is transcriptionally co-regulated with other ribosomal protein genes through conserved promoter elements that bind nuclear factors (PMID:8477735, PMID:8665930). RPL37A also directly crosslinks to poly(A)+ mRNA in living cells, suggesting a potential extraribosomal role in post-transcriptional regulation (PMID:22681889).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 1989 High

    Determination of the primary structure of L37a established it as a small 60S subunit protein whose NH2-terminal methionine is post-translationally removed, providing the foundation for all subsequent structural and functional studies.

    Evidence cDNA cloning confirmed by NH2-terminal amino acid sequencing of the purified rat protein

    PMID:2546769

    Open questions at the time
    • No information on how L37a contacts rRNA or other ribosomal proteins
    • Function within the ribosome beyond structural membership uncharacterized
  2. 1992 Medium

    Identification of a conserved C2-C2 zinc finger motif across vertebrate and lower eukaryotic orthologs suggested that L37a engages rRNA through zinc-mediated contacts, a hypothesis that persisted until structural resolution two decades later.

    Evidence Sequence analysis of chicken, rat, Dictyostelium, and Drosophila L37a cDNAs with motif annotation

    PMID:10571043 PMID:1380836 PMID:8722009 PMID:9836437

    Open questions at the time
    • Zinc binding and RNA interaction were inferred from sequence, not experimentally demonstrated
    • No mutagenesis of the zinc finger residues
  3. 1993 Medium

    Promoter dissection revealed that RPL37A transcription depends on a compact regulatory region containing multiple nuclear protein-binding sites shared with other ribosomal protein genes, establishing a basis for coordinate expression of the translational machinery.

    Evidence CAT reporter deletion assays and DNase I footprinting of the chicken RPL37A promoter

    PMID:8477735 PMID:8665930

    Open questions at the time
    • Identity of the transcription factors binding the footprinted sites was not determined
    • Whether coordinate regulation extends to mammalian RPL37A promoters was not tested
  4. 2012 Medium

    UV-crosslinking and mRNA interactome capture showed that RPL37A directly contacts poly(A)+ mRNA in living human cells, raising the possibility of an extraribosomal role in post-transcriptional regulation.

    Evidence PAR-CLIP-based mRNA interactome capture with quantitative proteomics in HEK293 cells

    PMID:22681889

    Open questions at the time
    • Whether mRNA contact occurs outside the ribosomal context was not distinguished
    • Specific mRNA targets and functional consequences of binding are unknown
  5. 2013 High

    Near-atomic cryo-EM structures of the human 80S ribosome placed RPL37A within the 60S subunit architecture, revealing its spatial relationship with metazoan-specific rRNA expansions and resolving the long-standing question of where the zinc finger domain sits in the assembled ribosome.

    Evidence Single-particle cryo-EM of the human 80S ribosome at near-atomic resolution, refined to ~2.9–3.6 Å in stable regions

    PMID:23636399 PMID:25901680

    Open questions at the time
    • No mutational or reconstitution data testing whether the zinc finger is required for 60S assembly
    • Dynamics of RPL37A during translation elongation not resolved
  6. 2022 Medium

    Endogenous GFP tagging confirmed cytoplasmic localization and stable 60S co-complex membership of RPL37A in human cells, corroborating structural and biochemical evidence from orthogonal approaches.

    Evidence CRISPR-mediated endogenous GFP tagging with confocal live-cell imaging and AP-MS in HEK293T cells (OpenCell)

    PMID:35271311

    Open questions at the time
    • No functional data on consequences of RPL37A depletion or mutation in human cells
    • Extraribosomal pools, if any, were not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Whether RPL37A has functionally significant extraribosomal activities — particularly in mRNA regulation — and whether its zinc finger motif is required for ribosome assembly or has additional roles remains unresolved.
  • No loss-of-function or gain-of-function studies in mammalian cells
  • Zinc finger mutagenesis has not been performed
  • No disease association established through direct genetic evidence

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0003723 RNA binding 1
Localization
GO:0005840 ribosome 4 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 2
Complex memberships
60S large ribosomal subunit80S ribosome

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 Rat ribosomal protein L37a was determined to contain 91 amino acids (NH2-terminal methionine removed post-translationally) with a molecular mass of 10,143 Da, establishing its primary structure as a component of the 60S ribosomal subunit. cDNA cloning and sequencing, confirmed by NH2-terminal amino acid sequencing of the purified protein European journal of biochemistry High 2546769
1992 Chicken ribosomal protein L37a contains a Cys2-Cys2 (C2C2) zinc finger motif, proposed to be involved in protein-RNA interaction within the ribosome. cDNA and genomic DNA sequencing with structural motif identification Biochimica et biophysica acta Medium 1380836
1993 The chicken RPL37A gene is 2,626 bp organized in four exons and three introns; the region from nucleotides -78 to -35 in the 5'-flanking region is critical for promoter activity and serves as a binding site for nuclear proteins, containing sequence elements common to many ribosomal protein gene promoters. Genomic sequencing, CAT reporter transfection assay, DNase I footprinting European journal of biochemistry Medium 8477735
1995 Mammalian (rat) L37a possesses a single C2-C2 zinc finger-like motif among its structural features, placing it within a subset of ribosomal proteins with zinc finger domains; the protein's sequence is evolutionarily related to counterparts in yeast and other eukaryotes. Comparative sequence analysis of 75 rat ribosomal proteins with structural motif annotation Biochemistry and cell biology Medium 8722009
1996 Nine protein-binding regions spanning positions -122 to +195 relative to the transcription start site regulate chicken RPL37A gene transcription; the region -120 to +168 is necessary for maximal promoter activity. These elements are conserved among vertebrate ribosomal protein gene promoters, suggesting coordinated regulation. CAT reporter transfection assay in chicken cell line, DNase I protection (footprinting) assay European journal of biochemistry Medium 8665930
1996 Chicken RPL37A maps to macrochromosome 7, demonstrating that the functionally related large-subunit ribosomal protein genes L5, L7a, and L37a are widely dispersed and not co-localized or linked in the chicken genome. Fluorescence in situ hybridization (FISH) on chicken chromosomes Gene Medium 8666239
1998 The Dictyostelium discoideum L37a ortholog (DdL37a) encodes a 91-amino-acid protein with high similarity to rat, human, and chicken L37a, contains the conserved C2-C2 zinc finger motif (Cys-X2-Cys-X14-Cys-X2-Cys), is present in single copy, and is expressed maximally in growing amoebae with levels decreasing coordinately with ribosome accumulation during development. Genomic DNA blot analysis, cDNA cloning/sequencing, RNA expression analysis Bioscience, biotechnology, and biochemistry Medium 9836437
1999 The Drosophila melanogaster homolog of L37a is a single-copy gene with four exons, ubiquitously expressed, encoding a 92-amino-acid protein 78% identical to mammalian L37a and containing the conserved C2-C2 zinc finger motif; it maps to cytological position 25C1-3, near the Minute mutation M(2)25C. Enhancer trap screen, cDNA/genomic sequencing, in situ hybridization for expression pattern, cytological mapping Gene Medium 10571043
2013 RPL37A (eL43 in current nomenclature) was resolved as a structural component of the human 80S ribosome large subunit in a near-atomic cryo-EM structure, revealing its spatial organization within the metazoan-specific ribosome architecture, including interaction with metazoan-specific ribosomal RNA expansions. High-resolution single-particle cryo-electron microscopy of human 80S ribosome Nature High 23636399
2015 The near-atomic structure of the human 80S ribosome (average 3.6 Å, reaching 2.9 Å in stable regions) confirmed RPL37A as a structural component of the 60S subunit, revealing atomic details of ribosomal protein-RNA interactions and subunit interface dynamics. Single-particle cryo-electron microscopy at near-atomic resolution with atomic model building Nature High 25901680
2012 RPL37A was identified as a component of the mRNA-bound proteome in human embryonic kidney cells, indicating it directly contacts mRNA transcripts and may participate in post-transcriptional gene regulation beyond its canonical ribosomal role. Photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification followed by quantitative proteomics (PAR-CLIP-based mRNA interactome) Molecular cell Medium 22681889
2005 RPL37A was identified as a participant in human protein-protein interaction networks through systematic yeast two-hybrid screening, with interactions validated by independent pull-down and co-immunoprecipitation assays. Automated yeast two-hybrid interaction mating of 4,456 baits × 5,632 preys; validation by pull-down and co-IP Cell Medium 16169070
2015 RPL37A was identified as part of the human 60S ribosomal complex network through affinity-purification mass spectrometry (BioPlex), confirming its stable co-complex associations within the human proteome in HEK293T cells. High-throughput affinity-purification mass spectrometry (AP-MS) in HEK293T cells covering 2,594 human proteins Cell Medium 26186194
2022 Endogenous GFP tagging and live-cell confocal imaging in the OpenCell project confirmed that RPL37A localizes to the cytoplasm consistent with its role in the 60S ribosomal subunit, with its interaction network matching ribosomal complex membership. Genome engineering for endogenous GFP tagging, confocal live-cell imaging, AP-MS interaction mapping Science Medium 35271311

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
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
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
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
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2013 Structures of the human and Drosophila 80S ribosome. Nature 481 23636399
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
2004 The molecular mechanics of eukaryotic translation. Annual review of biochemistry 396 15189156
2015 Structure of the human 80S ribosome. Nature 380 25901680
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2003 Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control. Cell 276 14567916
1995 Structure and evolution of mammalian ribosomal proteins. Biochemistry and cell biology = Biochimie et biologie cellulaire 265 8722009
2022 EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3. Molecular cancer 257 35031058
2010 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunology and cell biology 221 20458337
2016 A High-Density Map for Navigating the Human Polycomb Complexome. Cell reports 216 27705803
2015 ∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature 209 26618866
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
1993 The primary structure of L37--a rat ribosomal protein with a zinc finger-like motif. Biochemical and biophysical research communications 12 8484768
1991 Screening a yeast promoter library leads to the isolation of the RP29/L32 and SNR17B/RPL37A divergent promoters and the discovery of a gene encoding ribosomal protein L37. Gene 10 1840541
1989 The primary structure of rat ribosomal protein L37a. European journal of biochemistry 10 2546769
2020 Analysis of RPL37A, MTSS1, and HTRA1 expression as potential markers for pathologic complete response and survival. Breast cancer (Tokyo, Japan) 9 32951185
1993 The structure of the gene encoding chicken ribosomal protein L37a. European journal of biochemistry 9 8477735
1996 A characterization of transcriptional regulatory elements in chicken ribosomal protein L37a gene. European journal of biochemistry 8 8665930
1996 The intron-containing ribosomal protein-encoding genes L5, L7a and L37a are unlinked in chicken. Gene 8 8666239
1992 The primary structure of chicken ribosomal protein L37a. Biochimica et biophysica acta 7 1380836
1998 The characterization of two Dictyostelium discoideum genes encoding ribosomal proteins with sequence similarity to rat L27a and L37a. Bioscience, biotechnology, and biochemistry 4 9836437
2002 Characterization of cDNA encoding a L37a ribosomal protein from Taenia crassiceps and its potential use in phylogenetic reconstructions. Experimental parasitology 2 12594966
1999 Ribosomal Proteins S27E, P2, and L37A from Marine Invertebrates. Marine biotechnology (New York, N.Y.) 2 10373627
1999 An enhancer trap line identifies the Drosophila homolog of the L37a ribosomal protein. Gene 1 10571043
2022 The dedicated chaperones of eL43, Puf6 and Loc1 can also bind RPL43 mRNA and regulate the production of this ribosomal protein. Journal of biochemistry 0 34661244