Affinage

RPS27

Small ribosomal subunit protein eS27 · UniProt P42677

Length
84 aa
Mass
9.5 kDa
Annotated
2026-06-10
46 papers in source corpus 12 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/6 claims corpus-supported (83%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPS27 (eS27) is a zinc finger-containing structural protein of the 40S ribosomal small subunit, purified directly from ribosomes and required for normal pre-rRNA processing (PMID:947902, PMID:8441676, PMID:25424902). Beyond its ribosomal role, its N-terminal region binds the central acidic domain of MDM2 to form an MDM2–p53 triplex, competing with p53 for MDM2, inhibiting p53 ubiquitination, and extending p53 half-life; p53 in turn represses RPS27 expression, defining a feedback loop (PMID:21170087). RPS27 stability is itself controlled by post-translational modification: MDM2 neddylates RPS27 and NEDP1 deneddylates it, so that neddylation blockade shortens RPS27 half-life and modulates cancer-cell sensitivity to apoptosis (PMID:32779270). Genetic studies establish RPS27 in ribosomopathy and translational specialization: a loss-of-function frameshift causes Diamond-Blackfan anaemia with impaired erythropoiesis (PMID:25424902), and Rps27- versus its paralog Rps27l-containing ribosomes preferentially translate distinct mRNA subsets yet are functionally interchangeable provided total expression is maintained (PMID:37306301). RPS27 also acts as an mRNA-binding protein that selectively associates with a defined set of ribosomal-protein transcripts (PMID:40016701), and contacts the ribotoxic-stress kinase ZAKα at the ribosomal mRNA exit channel to participate in sensing translational impairment [PMID:bio_10.1101_2025.11.22.689755]. In cancer, RPS27 expression—altered by recurrent melanoma 5'UTR/promoter mutations—modulates proliferation, invasion, and metastatic capacity (PMID:24913145, PMID:31663663, PMID:38365771).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1976 High

    Established RPS27 as a genuine structural subunit of the small ribosomal subunit rather than a contaminant, the foundation for all subsequent work.

    Evidence Biochemical purification from rat liver 40S subunits by chromatography and SDS-PAGE

    PMID:947902

    Open questions at the time
    • Position within the assembled 40S and rRNA contacts not resolved
    • No functional role assigned beyond structural presence
  2. 1993 Medium

    Defined the primary structure and identified a C4-type zinc finger motif, raising the possibility of nucleic-acid interaction beyond a passive structural role.

    Evidence cDNA and amino acid sequencing of rat RPS27 plus metal-content analysis of ribosomes

    PMID:8441676

    Open questions at the time
    • Zinc finger function not tested by mutagenesis
    • No demonstration of DNA/RNA binding through the motif at this stage
  3. 2010 High

    Revealed an extra-ribosomal function in which RPS27 stabilizes p53 by competing for MDM2, connecting a ribosomal protein to tumor-suppressor regulation.

    Evidence Reciprocal Co-IP, domain-mapping pulldowns, in vivo ubiquitination assay, and p53 half-life measurements with siRNA

    PMID:21170087

    Open questions at the time
    • Whether free vs ribosome-bound RPS27 drives the interaction unclear
    • Structural basis of the N-terminus/MDM2 acidic-domain contact not defined
  4. 2014 Medium

    Linked RPS27 loss-of-function to Diamond-Blackfan anaemia and a defined pre-rRNA processing defect, establishing it as a ribosomopathy gene with erythroid relevance.

    Evidence Whole-exome sequencing of a patient, in vitro pre-rRNA processing assay, and zebrafish morpholino knockdown

    PMID:25424902

    Open questions at the time
    • Specific pre-rRNA cleavage step affected not mapped
    • Mechanism linking processing defect to erythroid failure not established
  5. 2014 Medium

    Identified recurrent melanoma 5'UTR mutations that expand the 5'TOP element, implicating altered growth-dependent translational control of RPS27 in cancer.

    Evidence Exome sequencing of melanoma cohorts with 5'TOP element functional analysis

    PMID:24913145

    Open questions at the time
    • Direct effect on RPS27 protein output in melanoma not quantified
    • Downstream oncogenic consequence not mechanistically traced
  6. 2019 Medium

    Showed RPS27 expression level functionally dictates melanoma cell behavior, with high RPS27 favoring proliferation/invasion and low RPS27 favoring survival and therapy resistance.

    Evidence Promoter mutation sequencing, reporter assays, and loss-of-function invasion/proliferation assays

    PMID:31663663

    Open questions at the time
    • Molecular effectors of the phenotypic switch unknown
    • Whether effects are ribosomal or extra-ribosomal not distinguished
  7. 2020 Medium

    Defined neddylation as a post-translational switch controlling RPS27 stability, identifying MDM2 as writer and NEDP1 as eraser and linking RPS27 levels to apoptotic sensitivity.

    Evidence Neddylation assays, CHX-chase half-life measurement, knockdown/overexpression, and MLN4924 apoptosis assays

    PMID:32779270

    Open questions at the time
    • Neddylation acceptor site(s) on RPS27 not mapped
    • Relationship between neddylation and the MDM2/p53 axis not resolved
  8. 2022 Low

    Suggested RPS27 overexpression reshapes inflammatory/immune and apoptotic gene programs and alternative splicing in thyroid cancer.

    Evidence Overexpression RNA-seq with splicing analysis and qRT-PCR validation

    PMID:35546566

    Open questions at the time
    • Single overexpression transcriptomics study without direct binding or epistasis
    • No demonstration of direct regulation of the affected genes
  9. 2023 High

    Demonstrated that Rps27 and Rps27l mark specialized ribosomes translating distinct mRNA subsets yet are functionally interchangeable when total expression is balanced, clarifying paralog roles.

    Evidence Endogenous tagging, ribosome profiling, and genetic knockin rescue in mouse knockouts

    PMID:37306301

    Open questions at the time
    • Mechanism conferring mRNA preference not defined
    • Whether specialization matters in human disease unresolved
  10. 2024 Medium

    Provided in vivo evidence that RPS27 levels drive prostate cancer liver metastasis through selective regulation of progression-associated genes.

    Evidence Intrasplenic xenograft metastasis model with gain/loss of function and mRNA sequencing

    PMID:38365771

    Open questions at the time
    • Direct targets driving metastasis not validated
    • Distinction between translational and signaling mechanisms unclear
  11. 2025 Medium

    Mapped RPS27 as an mRNA-binding protein selectively associating with ribosomal-protein transcripts in Kaposi's sarcoma cells, expanding its RNA-regulatory repertoire.

    Evidence iRIP-seq, RNA-seq, and knockdown with migration/invasion/tube-formation assays

    PMID:40016701

    Open questions at the time
    • Whether binding occurs as free protein or within ribosomes unknown
    • Functional consequence of binding each target transcript not dissected
  12. 2025 Medium

    Placed RPS27 at the ribosomal mRNA exit channel as a direct contact for the ribotoxic-stress kinase ZAKα, implicating it in sensing translational impairment.

    Evidence AlphaFold3 prediction, CLIP, and biochemical interaction assays (preprint)

    PMID:bio_10.1101_2025.11.22.689755

    Open questions at the time
    • Single preprint not yet peer-reviewed
    • Contribution of RPS27 specifically (vs RACK1/18S) to ZAKα activation not isolated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RPS27's ribosomal, RNA-binding, and extra-ribosomal (p53/MDM2, ZAKα) functions are coordinated, and whether they share a structural basis, remains unresolved.
  • No structure of RPS27 in complex with MDM2 or ZAKα
  • Mechanistic link between neddylation, p53 stabilization, and translational specialization undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005840 ribosome 2
Pathway
R-HSA-392499 Metabolism of proteins 2 R-HSA-8953854 Metabolism of RNA 2
Partners
MDM2NEDP1RACK1RPS27LZAKALPHA
Complex memberships
40S ribosomal subunit

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Rat ribosomal protein S27 (RPS27) has 83 amino acids and contains a zinc finger-like motif (C4-type), consistent with zinc-binding and potential DNA/RNA interaction. Ribosomes and ribosomal subunits were shown to contain zinc and iron. cDNA sequencing, amino acid sequence determination, hybridization analysis Nucleic acids research Medium 8441676
1976 RPS27 was isolated and purified from the 40S ribosomal subunit of rat liver ribosomes, establishing it as a bona fide structural component of the small ribosomal subunit. Ion exchange chromatography, gel filtration, SDS-PAGE, amino acid composition analysis The Journal of biological chemistry High 947902
2010 RPS27 binds to the central acidic domain of MDM2 via its N-terminal region, forming an in vivo triplex with MDM2-p53. RPS27 competes with p53 for MDM2 binding, inhibits MDM2-mediated p53 ubiquitination, and increases p53 levels by extending p53 protein half-life. RPS27 expression is repressed by p53. Co-immunoprecipitation, domain-mapping pulldown, ubiquitination assay, siRNA knockdown, p53 half-life measurements, reporter assay Oncogene High 21170087
2014 Loss-of-function frameshift deletion in RPS27 was identified in a Diamond-Blackfan anaemia patient. In vitro knockdown of RPS27 disrupted pre-ribosomal RNA processing. Zebrafish rps27 morphants showed impaired erythrocyte production and developmental defects. Whole-exome sequencing, in vitro knockdown, pre-rRNA processing assay, zebrafish morpholino knockdown model British journal of haematology Medium 25424902
2014 A recurrent hotspot mutation in the 5' UTR of RPS27 (~10% of melanomas) expands the 5'TOP element, a regulatory motif that controls expression of ribosomal protein transcripts in a growth-dependent manner, potentially sensitizing RPS27 mRNA to growth-mediated translational regulation. Exome sequencing of melanoma cohorts, 5'TOP element functional analysis Oncotarget Medium 24913145
2020 Both RPS27 and RPS27L are subjected to neddylation by MDM2 E3 ubiquitin ligase, and deneddylation by NEDP1. Blockage of neddylation with MLN4924 destabilizes RPS27 by shortening its protein half-life. Knockdown of RPS27 sensitizes cancer cells to MLN4924-induced apoptosis, while ectopic RPS27 expression desensitizes cells. Neddylation assay, protein half-life measurement (CHX chase), siRNA knockdown, ectopic overexpression, apoptosis assay FASEB journal Medium 32779270
2023 Rps27 and Rps27l are paralogous ribosomal proteins that arose by vertebrate whole-genome duplication. They have inversely correlated expression across mouse cell types. Rps27- and Rps27l-containing ribosomes preferentially associate with different subsets of mRNAs (specialized ribosomes). Homozygous loss of either is lethal at different developmental stages, but expressing one protein from the other's locus fully rescues lethality, demonstrating the two proteins are functionally equivalent but must achieve appropriate total expression across cell types. Endogenous protein tagging, ribosome profiling/RNA association, genetic knockin rescue, mouse knockout studies eLife High 37306301
2025 ZAKα (the ribotoxic stress response kinase) directly interacts with RPS27 at the mRNA exit channel of elongating ribosomes, as well as with RACK1 and 18S rRNA helix-26. This interaction is stabilized by mRNA stasis and is part of a mechanism by which ZAKα senses translational impairment to activate p38/JNK signaling. AlphaFold3 structural prediction, RNA crosslinking and immunoprecipitation (CLIP), biochemical interaction assays bioRxivpreprint Medium bio_10.1101_2025.11.22.689755
2019 Two recurrent mutations in the RPS27 promoter were associated with decreased RPS27 mRNA levels in vitro in melanoma. Loss-of-function experiments showed that high RPS27 status provides increased proliferative and invasive capacities, while low RPS27 confers survival advantage under low attachment conditions and resistance to therapy. Targeted sequencing, in vitro reporter assay, loss-of-function (siRNA/shRNA), transwell invasion/proliferation assay Pigment cell & melanoma research Medium 31663663
2022 RPS27 overexpression in thyroid cancer cells selectively regulates expression of inflammatory/immune response genes and alternative splicing of genes in the TRIF-dependent toll-like receptor signaling pathway and apoptotic process, as revealed by transcriptome analysis. RPS27 overexpression, RNA-seq transcriptomics, alternative splicing analysis, qRT-PCR validation Advances in clinical and experimental medicine Low 35546566
2025 RPS27 acts as an RNA-binding protein in Kaposi's sarcoma cells and selectively binds a set of ribosomal protein mRNAs (including RPL8, RPL13, RPS2, RPS4X, RPS13, RPS18, RPS21, and others associated with viral transcription). RPS27 inhibition promotes cellular proliferation, migration, invasion, and angiogenesis of HUVECs. iRIP-seq (improved RNA immunoprecipitation sequencing), RNA-seq, siRNA knockdown, transwell migration/invasion assay, tube formation assay BMC cancer Medium 40016701
2024 RPS27 overexpression promotes prostate cancer liver metastasis in vivo, while RPS27 knockdown significantly reduces it. RPS27 promotes metastasis by selectively enhancing expression of genes involved in prostate cancer progression as revealed by mRNA sequencing. Intrasplenic xenograft injection (in vivo metastasis model), transwell migration/invasion assay, RPS27 overexpression and knockdown, mRNA sequencing Cancer & metabolism Medium 38365771

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Ribosomal protein S27-like and S27 interplay with p53-MDM2 axis as a target, a substrate and a regulator. Oncogene 115 21170087
2014 Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia. British journal of haematology 84 25424902
1993 Zinc finger-like motifs in rat ribosomal proteins S27 and S29. Nucleic acids research 75 8441676
1976 The isolation of eukaryotic ribosomal proteins. The purification and characterization of the 40 S ribosomal subunit proteins S2, S3, S4, S5, S6, S7, S8, S9, S13, S23/S24, S27, and S28. The Journal of biological chemistry 72 947902
2017 Aerobic and heterotrophic nitrogen removal by Enterobacter cloacae CF-S27 with efficient utilization of hydroxylamine. Bioresource technology 68 28242385
1977 Isolation of eukaryotic ribosomal proteins. Purification and characterization of the 40 S ribosomal subunit proteins Sa, Sc, S3a, S3b, S5', S9, S10, S11, S12, S14, S15, S15', S16, S17, S18, S19, S20, S21, S26, S27', and S29. The Journal of biological chemistry 60 925037
2015 Complete Genome Sequence of Porcine Deltacoronavirus Strain CH/Sichuan/S27/2012 from Mainland China. Genome announcements 55 26337879
2007 Ribosomal protein S27-like, a p53-inducible modulator of cell fate in response to genotoxic stress. Cancer research 54 18056458
2014 Ribosomal protein S27-like is a physiological regulator of p53 that suppresses genomic instability and tumorigenesis. eLife 47 25144937
2014 A highly recurrent RPS27 5'UTR mutation in melanoma. Oncotarget 41 24913145
2008 A xylanase with high pH stability from Streptomyces sp. S27 and its carbohydrate-binding module with/without linker-region-truncated versions. Applied microbiology and biotechnology 40 19107475
2013 Ribosomal protein S27-like in colorectal cancer: a candidate for predicting prognoses. PloS one 36 23826192
2018 Ribosomal protein S27-like regulates autophagy via the β-TrCP-DEPTOR-mTORC1 axis. Cell death & disease 31 30425236
2010 Genetic and biochemical characterization of a protease-resistant mesophilic β-mannanase from Streptomyces sp. S27. Journal of industrial microbiology & biotechnology 28 20686915
2019 Biodegradation of malachite green by an endophytic bacterium Klebsiella aerogenes S27 involving a novel oxidoreductase. Applied microbiology and biotechnology 27 30613897
2009 Cloning, characterization, and antifungal activity of an endo-1,3-beta-D: -glucanase from Streptomyces sp. S27. Applied microbiology and biotechnology 27 19697016
2008 Cloning, expression, and characterization of a new Streptomyces sp. S27 xylanase for which xylobiose is the main hydrolysis product. Applied biochemistry and biotechnology 27 19002659
2020 Ribosomal Protein S27/Metallopanstimulin-1 (RPS27) in Glioma-A New Disease Biomarker? Cancers 24 32349320
2001 Differential expression of metallopanstimulin/S27 ribosomal protein in hepatic regeneration and neoplasia. Cancer detection and prevention 24 11425264
2000 Evolutionarily distinct classes of S27 ribosomal proteins with differential mRNA expression in rat hypothalamus. Journal of neurochemistry 24 10820185
2019 RPS27, a sORF-Encoded Polypeptide, Functions Antivirally by Activating the NF-κB Pathway and Interacting With Viral Envelope Proteins in Shrimp. Frontiers in immunology 23 31921103
1997 Differential expression of metallopanstimulin/S27 ribosomal protein in melanocytic lesions of the skin. Journal of cutaneous pathology 21 9404850
2018 Inactivation of ribosomal protein S27-like confers radiosensitivity via the Mdm2-p53 and Mdm2-MRN-ATM axes. Cell death & disease 18 29396424
2011 Cloning and characterization of a new β-mannosidase from Streptomyces sp. S27. Enzyme and microbial technology 18 22112512
2012 An alkaline-active and alkali-stable pectate lyase from Streptomyces sp. S27 with potential in textile industry. Journal of industrial microbiology & biotechnology 17 22278674
2020 Neddylation modification of ribosomal protein RPS27L or RPS27 by MDM2 or NEDP1 regulates cancer cell survival. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 32779270
2011 Conservation of multifunctional ribosomal protein metallopanstimulin-1 (RPS27) through complex evolution demonstrates its key role in growth regulation in Archaea, eukaryotic cells, DNA repair, translation and viral replication. Cancer genomics & proteomics 16 21518817
1980 Purification of Drosophila ribosomal proteins. Isolation of proteins S8, S13, S14, S16, S19, S20/L24, S22/L26, S24, S25/S27, S26, S29, L4, L10/L11, L12, L13, L16, L18, L19, L27, 1, 7/8, 9, and 11. Biochemistry 16 6773542
2012 Increased serum level of RPMPS-1/S27 protein in patients with various types of cancer is useful for the early detection, prevention and therapy. Cancer genomics & proteomics 15 22798506
2022 Identification of meroterpenoids from Bipolaris victoriae S27 and their potential activity against tumor metastasis and inhibition of the NF-κB signaling pathway. Phytochemistry 13 35427653
2019 Functional analysis of RPS27 mutations and expression in melanoma. Pigment cell & melanoma research 13 31663663
2020 Inactivation of ribosomal protein S27-like impairs DNA interstrand cross-link repair by destabilization of FANCD2 and FANCI. Cell death & disease 12 33051438
2019 A novel potent autophagy inhibitor ECDD-S27 targets vacuolar ATPase and inhibits cancer cell survival. Scientific reports 12 31235856
2019 Molecular cloning, expression and impact of ribosomal protein S-27 silencing in Haemaphysalis longicornis (Acari: Ixodidae). Experimental parasitology 12 31887531
1996 Primary structures and sequence analysis of human ribosomal proteins L39 and S27. Biochemistry and molecular biology international 10 8908372
2024 High-fat diet promotes prostate cancer metastasis via RPS27. Cancer & metabolism 9 38365771
2023 Subfunctionalized expression drives evolutionary retention of ribosomal protein paralogs Rps27 and Rps27l in vertebrates. eLife 9 37306301
2012 Enhanced expression of tubulin-specific chaperone protein A, mitochondrial ribosomal protein S27, and the DNA excision repair protein XPACCH in the song system of juvenile male zebra finches. Developmental neurobiology 8 21780305
2022 RPS27 selectively regulates the expression and alternative splicing of inflammatory and immune response genes in thyroid cancer cells. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 7 35546566
2016 A Novel Marker for Purkinje Cells, Ribosomal Protein MPS1/S27: Expression of MPS1 in Human Cerebellum. Cancer genomics & proteomics 5 26708598
2024 Impact of potential biomarkers, SNRPE, COX7C, and RPS27, on idiopathic Parkinson's disease. Genes & genomics 4 39467967
2025 Single-cell multi-omics elucidates the role of RPS27-RPS24 fusion gene in osteosarcoma chemoresistance and metabolic regulation. Cell death discovery 3 40280903
1991 Biochemical and genetic characterization of esterase-27 (ES-27), the major plasma cholinesterase of the house mouse (Mus musculus). Genetical research 3 2040456
2025 Exploration of RNA-binding proteins identified RPS27 as a potential regulator associated with Kaposi's sarcoma development. BMC cancer 2 40016701
2005 Metallopanstimulin / S27 Ribosomal Antigen Expression in Stages I and II Breast Cancer: its Relationship with Clinicopathologic Factors. Cancer genomics & proteomics 2 31394666
2001 [Complementation analysis of mutants of the associative bacteria Azospirillum brasilense Sp245 and S27, defective in mobility and flagellation]. Genetika 0 11253425

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