Affinage

RPL7A

Large ribosomal subunit protein eL8 · UniProt P62424

Length
266 aa
Mass
30.0 kDa
Annotated
2026-06-10
26 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL7A (originally Surf-3/L7a) is a basic protein component of the 60S large ribosomal subunit and is essential for ribosome function and viability (PMID:2648130, PMID:2046660). It is a nucleolar protein whose targeting is encoded by three distinct domains, each carrying an NLS, with nucleolar accumulation requiring a core domain (aa 52–100) acting cooperatively with an additional basic stretch — a feature consistent with protein–protein or protein–nucleic acid contacts (PMID:9030593). RPL7A binds RNA through two domains, RNAB1 (aa 52–100) and RNAB2 (aa 101–161), the latter mapped in complex with a G-rich poly(G) oligonucleotide; RNAB1 lacks recognizable nucleic-acid-binding motifs (PMID:15361074). Its introns host box C/D antisense snoRNAs (U24 and three U36 variants) that guide site-specific 2'-O-ribose methylation of rRNA, coupling RPL7A expression to ribosome biogenesis (PMID:9703018). Beyond the core ribosomal role, RPL7A is engaged in stress and disease contexts: under ischemic stress it is bound in the nucleus by FKBP25 (PMID:29969783), and in lung adenocarcinoma it promotes proliferation, migration, and invasion by regulating a circRANBP17–UPF1 complex that destabilizes SIRT6 mRNA, lowering SIRT6 and altering lipid metabolism and AKT activity (PMID:41372808).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1990 High

    Establishing that the Surf-3/trk-2h gene product is the 60S ribosomal protein L7a fixed the molecular identity and nucleolar location of an otherwise enigmatic gene product.

    Evidence Anti-peptide immunoblotting of 2D-resolved ribosomal proteins, in vitro translation, and immunofluorescence in mammalian cells

    PMID:2403926 PMID:2648130

    Open questions at the time
    • Did not define the protein's position or function within the assembled 60S subunit
    • No structural model of L7a–rRNA contacts
  2. 1991 High

    Yeast genetics established that L7a (homolog L4) is essential, tying the protein directly to functional ribosome production.

    Evidence Double gene disruption (lethal) and single-paralog disruption (growth defect) in S. cerevisiae with identity confirmed by 2D gel and direct sequencing

    PMID:2046660

    Open questions at the time
    • Did not resolve which step of ribosome assembly or translation requires the protein
    • Mammalian essentiality inferred only by homology
  3. 1992 Medium

    Mapping conserved Box A/Box B promoter elements and a TATA-less pyrimidine-rich start explained how RPL7A transcription is controlled like other ribosomal protein genes.

    Evidence EMSA with nuclear extracts plus promoter-deletion reporter assays in mammalian and avian systems

    PMID:1630908 PMID:8482538

    Open questions at the time
    • Identity of the bound nuclear factors not determined
    • No link to coordinate ribosomal protein gene regulation in vivo
  4. 1997 High

    Dissecting nuclear/nucleolar targeting signals showed that localization is encoded by three cooperative domains rather than a single NLS, implying that nucleolar retention depends on macromolecular interactions.

    Evidence Deletion mutagenesis of L7a–beta-galactosidase fusions with immunofluorescence in HeLa cells

    PMID:9030593

    Open questions at the time
    • The cooperating nucleolar binding partners (RNA or protein) were not identified
    • Did not separate import from retention mechanisms
  5. 1998 Medium

    Discovery of intron-encoded box C/D snoRNAs (U24, U36 variants) revealed that the RPL7A locus directly contributes guides for rRNA 2'-O-methylation, embedding it in ribosome biogenesis beyond its protein product.

    Evidence Comparative genomics and Northern blotting across human, chicken, and mouse introns

    PMID:9703018

    Open questions at the time
    • Functional consequence of individual U36 variants on specific rRNA sites not tested
    • Did not establish coupling between host-gene splicing and snoRNA output
  6. 2005 High

    Mapping two RNA-binding domains and a poly(G) interaction interface defined the biochemical basis of RPL7A's RNA contacts, including a domain lacking canonical motifs.

    Evidence In vitro RNA-binding with recombinant domains, limited proteolysis, cross-linking, and mass spectrometry using a 30-mer poly(G)

    PMID:15361074

    Open questions at the time
    • The physiological RNA target within rRNA was not identified
    • RNAB1 binding mode remains structurally undefined
  7. 2017 Medium

    Paralog-swap experiments in yeast distinguished dosage from isoform identity, showing most Rpl7 phenotypes track protein/ribosome level while Ty1 cDNA accumulation also depends on isoform or intron-encoded snoRNA.

    Evidence Chimeric allele exchange with retrotransposition, mRNA localization, and growth assays in S. cerevisiae

    PMID:28007835

    Open questions at the time
    • Did not separate the isoform contribution from the intron-encoded snoRNA contribution
    • Relevance of Ty1/ASH1 phenotypes to mammalian RPL7A unknown
  8. 2018 Medium

    Identifying a stress-induced FKBP25–L7a interaction in the nucleus extended RPL7A's relevance beyond constitutive translation into endothelial ischemic-stress responses.

    Evidence Reciprocal co-immunoprecipitation and FRET in endothelial cells under oxygen-glucose deprivation, with FKBP25 overexpression protection

    PMID:29969783

    Open questions at the time
    • Functional consequence of the interaction for L7a or ribosome activity not defined
    • Single lab; mechanism of the protective effect unresolved
  9. 2025 Medium

    A circRANBP17–UPF1–SIRT6 axis defined a non-canonical, tumor-promoting role for RPL7A in lung adenocarcinoma, linking it to lipid metabolism and AKT signaling.

    Evidence RPL7A knockdown, RNA immunoprecipitation, mRNA stability and dual-luciferase assays, FISH, and in vitro/in vivo functional assays in LUAD models

    PMID:41372808

    Open questions at the time
    • How RPL7A controls circRANBP17 levels mechanistically is not resolved
    • Whether this role is separable from its ribosomal function is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how RPL7A's structural ribosomal function is integrated with its extra-ribosomal activities (FKBP25 stress complex, circRANBP17/SIRT6 oncogenic axis) and whether these reflect free versus ribosome-bound pools.
  • No structure of full-length RPL7A in the assembled 60S subunit
  • No determination of which RPL7A pool mediates non-ribosomal functions
  • No mechanistic link between RNA-binding domains and the circRNA/mRNA-regulatory roles

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 2 GO:0005840 ribosome 2
Pathway
R-HSA-392499 Metabolism of proteins 2 R-HSA-8953854 Metabolism of RNA 1
Partners
FKBP25UPF1
Complex memberships
60S large ribosomal subunit

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 The Surf-3 gene product (RPL7A) was identified as a 32-kDa ribosomal protein located in the 60S ribosomal subunit, established by anti-peptide serum immunofluorescence, immunoblotting of mouse cell components, in vitro translation of Surf-3 cDNA hybrid-selected mRNA, 2D-gel analysis, and homology with rat ribosomal peptide sequence. Anti-peptide serum immunofluorescence, immunoblotting, in vitro translation, 2D-gel electrophoresis, biochemical fractionation Molecular and cellular biology High 2648130
1990 RPL7A (the 30 kDa protein encoded by the trk-2h N-terminal activating sequence) was identified as ribosomal large subunit protein L7a by Western immunoblotting of 2D-electrophoretically resolved ribosomal proteins; the protein shows intense nucleolar staining by immunofluorescence and has high basic amino acid content. Western blotting of 2D-resolved ribosomal proteins, immunofluorescence with antipeptide antibodies The EMBO journal High 2403926
1991 The yeast (S. cerevisiae) L4 gene is the homolog of mammalian RPL7A (Surf-3/L7a); disruption of both L4 paralogs is lethal likely due to inability to produce functional ribosomes, while disruption of L4-1 alone results in very small colonies, establishing an essential role for this protein in ribosome function. Gene disruption (knockout), colony growth assay, in vitro translation of hybrid-selected mRNA, 2D gel analysis, direct amino acid sequencing Molecular & general genetics : MGG High 2046660
1993 The minimal promoter element required for human RPL7A transcription was identified as 130 bp of the 5'-flanking region; the gene lacks a canonical TATA sequence and has a C as the major transcriptional start point in a pyrimidine-rich region, features shared with other mammalian ribosomal protein genes. Promoter deletion analysis, transcription reporter assay Gene Medium 8482538
1992 Two conserved promoter elements (Box A: nts -56 to -39; Box B: nts -25 to -4) in the rpL7a 5' upstream region bind distinct nuclear factors from mouse nuclear extracts, and both elements are functionally conserved between mammals and birds; constructs containing only 56 bp of upstream DNA plus the first 25 bp exon support efficient transcription without requiring first intron sequences. Electrophoretic mobility shift assay (EMSA), competition assay with homologous sequences, in vivo transcription reporter assay Nucleic acids research Medium 1630908
1997 Three distinct domains of human RPL7A mediate nuclear targeting: domain I (aa 23–51), domain II (aa 52–100), and domain III (aa 101–220), each containing at least one NLS. Domain II is necessary but not sufficient for nucleolar targeting; nucleolar accumulation requires domain II plus an additional basic domain (NLS or basic stretch), indicating cooperative protein–protein or protein–nucleic acid interactions. Transient expression of L7a–beta-galactosidase fusion proteins with deletion mutants in HeLa cells, indirect immunofluorescence The Journal of biological chemistry High 9030593
2005 Human RPL7A contains two RNA-binding domains: RNAB1 (aa 52–100) and RNAB2 (aa 101–161). RNAB1 lacks known nucleic-acid-binding motifs and may represent a novel class. The topology of the L7a–RNA complex was mapped using limited proteolysis, cross-linking, and mass spectrometry of the recombinant aa 101–161 domain with a 30-mer poly(G) oligonucleotide. L7a interacts in vitro with a presumably G-rich RNA structure. In vitro RNA-binding assay, deletion mutagenesis, limited proteolysis, chemical cross-linking, mass spectrometry The Biochemical journal High 15361074
2011 The N-terminal domain of human RPL7A was crystallized and X-ray diffraction data collected to 3.5 Å resolution (tetragonal space group P4(1)22 or P4(3)22; unit-cell a = b = 92.28 Å, c = 236.59 Å), providing preliminary structural characterization. The paper also notes that RPL7A interacts with thyroid hormone receptor (THR) and retinoic acid receptor (RAR) to inhibit their activities. X-ray crystallography (preliminary), recombinant protein expression in E. coli Acta crystallographica. Section F, Structural biology and crystallization communications Low 21505254
2018 Under ischemic stress (oxygen-glucose deprivation or peroxynitrite treatment), FKBP25 translocates to the nucleus in endothelial cells and interacts with 60S ribosomal protein L7a, as demonstrated by co-immunoprecipitation and FRET; overexpression of FKBP25 protects endothelial cells against OGD injury. Co-immunoprecipitation, fluorescence resonance energy transfer (FRET), Western blot, immunofluorescence, overexpression Cellular physiology and biochemistry Medium 29969783
2017 In S. cerevisiae, paralog-specific phenotypes of RPL7A vs RPL7B (tunicamycin sensitivity, ASH1 mRNA localization, Ty1 retrotransposon mobility) are driven primarily by differences in protein/ribosome levels rather than isoform identity; however, Ty1 cDNA accumulation is influenced by both level and isoform (or intron-encoded snoRNA) expressed. Depletion of Rpl7 strongly affects Ty1 RNA localization but minimally affects Ty1 Gag protein synthesis. Paralog swap (chimeric alleles), quantitative phenotypic assays (tunicamycin growth, mRNA localization, retrotransposition assay), Western blot, Northern blot G3 (Bethesda, Md.) Medium 28007835
1998 U24 and U36 snoRNAs are encoded within introns of the rpL7a gene in human, chicken, and mouse; these box C/D antisense snoRNAs guide site-specific ribose methylation of rRNA. In mammals, three U36 variants reside in introns 4, 5, and 6 of rpL7a, with unique structural features distinct from non-mammalian variants. Sequence analysis, comparative genomics, Northern blotting (snoRNA identification within introns) DNA and cell biology Medium 9703018
2025 RPL7A promotes lung adenocarcinoma progression by regulating circRANBP17, which forms a complex with UPF1 to destabilize SIRT6 mRNA, thereby reducing SIRT6 protein levels and altering lipid metabolism and AKT pathway activity; RPL7A knockdown inhibits LUAD cell migration, invasion, and proliferation. RPL7A knockdown, mRNA stability assays, RNA immunoprecipitation, fluorescence in situ hybridization, dual luciferase reporter assay, in vitro and in vivo functional assays Cellular & molecular biology letters Medium 41372808

Source papers

Stage 0 corpus · 26 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Several genes encoding ribosomal proteins are over-expressed in prostate-cancer cell lines: confirmation of L7a and L37 over-expression in prostate-cancer tissue samples. International journal of cancer 94 9724090
1990 Oncogenic activation of the human trk proto-oncogene by recombination with the ribosomal large subunit protein L7a. The EMBO journal 80 2403926
1997 Different domains cooperate to target the human ribosomal L7a protein to the nucleus and to the nucleoli. The Journal of biological chemistry 48 9030593
1989 Ribosomal protein L7a is encoded by a gene (Surf-3) within the tightly clustered mouse surfeit locus. Molecular and cellular biology 48 2648130
2005 An ancient spliceosomal intron in the ribosomal protein L7a gene (Rpl7a) of Giardia lamblia. BMC evolutionary biology 45 16109161
1991 The organization and expression of the human L7a ribosomal protein gene. Biochimica et biophysica acta 35 1756182
1992 Functional elements of the ribosomal protein L7a (rpL7a) gene promoter region and their conservation between mammals and birds. Nucleic acids research 34 1630908
2005 Ribosomal protein L7a binds RNA through two distinct RNA-binding domains. The Biochemical journal 29 15361074
1990 The mouse rpL7a gene is typical of other ribosomal protein genes in it's 5' region but differs in being located in a tight cluster of CpG-rich islands. Nucleic acids research 28 2216707
1991 The organization and expression of the Saccharomyces cerevisiae L4 ribosomal protein genes and their identification as the homologues of the mammalian ribosomal protein gene L7a. Molecular & general genetics : MGG 27 2046660
2001 Modulation of expression of ribosomal protein L7a (rpL7a) by ethanol in human breast cancer cells. Breast cancer research and treatment 25 11759826
2009 Down-regulation of ribosomal protein L7A in human osteosarcoma. Journal of cancer research and clinical oncology 23 19125294
2000 Ribosomal protein L7a gene is up-regulated but not fused to the tyrosine kinase receptor as chimeric trk oncogene in human colorectal carcinoma. International journal of oncology 21 10717245
1993 Human L7a ribosomal protein: sequence, structural organization, and expression of a functional gene. Gene 21 8482538
1989 Localization of the Surfeit gene cluster containing the ribosomal protein gene L7a to chromosome bands 9q33-34. Annals of human genetics 17 2596824
1995 Surf5: a gene in the tightly clustered mouse surfeit locus is highly conserved and transcribed divergently from the rpL7A (Surf3) gene. Genomics 16 8586415
1995 The genomic organization of the region containing the Drosophila melanogaster rpL7a (Surf-3) gene differs from those of the mammalian and avian Surfeit loci. Molecular and cellular biology 15 7739520
1993 The complete nucleotide sequence of chicken ribosomal protein L7a gene and the multiple factor binding sites in its 5'-flanking region. Biochimie 15 8274530
2017 Paralog-Specific Functions of RPL7A and RPL7B Mediated by Ribosomal Protein or snoRNA Dosage in Saccharomyces cerevisiae. G3 (Bethesda, Md.) 14 28007835
1996 The intron-containing ribosomal protein-encoding genes L5, L7a and L37a are unlinked in chicken. Gene 8 8666239
2010 The Nop5-L7A-fibrillarin RNP complex and a novel box C/D containing sRNA of Halobacterium salinarum NRC-1. Biochemical and biophysical research communications 7 20206603
2018 Elucidation of the FKBP25-60S Ribosomal Protein L7a Stress Response Signaling During Ischemic Injury. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 6 29969783
1998 Evolution of U24 and U36 snoRNAs encoded within introns of vertebrate rpL7a gene homologs: unique features of mammalian U36 variants. DNA and cell biology 6 9703018
2011 Crystallization and preliminary X-ray crystallographic studies of the N-terminal domain of human ribosomal protein L7a (RPL7a). Acta crystallographica. Section F, Structural biology and crystallization communications 2 21505254
1998 The gene for ribosomal protein L7a-1 in Schizosaccharomyces pombe contains an intron after the initiation codon. Biochimica et biophysica acta 2 9565672
2025 Ribosomal protein RPL7A modulates lung adenocarcinoma progression via circRANBP17-UPF1-mediated SIRT6 degradation. Cellular & molecular biology letters 1 41372808

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