Affinage

RPS21

Small ribosomal subunit protein eS21 · UniProt P63220

Length
83 aa
Mass
9.1 kDa
Annotated
2026-06-10
57 papers in source corpus 17 papers cited in narrative 17 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

RPS21/eS21 is a small-subunit ribosomal protein that contacts the 3' end of small-subunit rRNA and is required for natural mRNA translation initiation and for small-subunit rRNA maturation and 40S/30S assembly (PMID:7028483, PMID:14627813). In bacteria, S21 is required for translation initiation on natural mRNAs but not for poly(U)- or AUG-directed model reactions, because it renders the 3' terminus of 16S rRNA accessible for Shine-Dalgarno base-pairing with mRNA; removing S21 abolishes both 3'-end oligonucleotide binding and mRNA acceptance, and re-adding it restores them (PMID:7028483, PMID:7232220). Cross-linking and neutron-scattering studies place S21 in direct contact with 16S rRNA at the 690–724 region and at the 3'-terminal nucleotides, positioning it at the decoding/initiation surface of the 30S subunit, where mRNA binding and subunit joining drive conformational rearrangements of this region (PMID:2437528, PMID:2437527, PMID:3005967, PMID:6378636, PMID:3288761). In eukaryotes, RPS21 is required for 3'-end maturation of 18S rRNA and formation of active 40S subunits: in budding yeast its loss reduces free 40S subunits and disrupts rRNA processing identically to Rps0 loss, and as part of the S0-cluster (with Rps0/uS2 and Rps2/uS5) it recruits the processing factor Nob1 and enables central pseudoknot folding in cytoplasmic SSU precursors (PMID:14627813, PMID:36996028). RPS21 physically partners with the ribosome-associated protein LBP/p40 (stubarista/Sta in Drosophila) (PMID:10022917, PMID:10079194).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1981 High

    Established that S21 is functionally specialized for the initiation step on real mRNAs rather than being a generic structural subunit, by showing it is dispensable for model-template translation but essential for natural mRNA initiation.

    Evidence In vitro reconstitution and antibody inactivation of S21-deficient 30S subunits with mRNA-dependent initiation assays in E. coli

    PMID:7028483

    Open questions at the time
    • Did not resolve the molecular basis by which S21 enables mRNA binding
    • Limited to bacterial system
  2. 1981 High

    Provided the mechanism for S21's initiation role by showing it makes the 3' end of 16S rRNA accessible for Shine-Dalgarno pairing, linking a structural rRNA effect to mRNA acceptance.

    Evidence 3'-end labeling, oligonucleotide probing, and reconstitution of S21-depleted 30S subunits in E. coli

    PMID:7232220

    Open questions at the time
    • Indirect inference of conformational state from oligonucleotide accessibility
    • No high-resolution structure
  3. 1986 Medium

    Mapped the physical contacts of S21 on 16S rRNA, defining where on the subunit S21 exerts its effect on the 3' end and decoding region.

    Evidence Multiple chemical cross-linking reagents (bis-chloroethyl-methylamine, azidophenyl acetimidate, 2-iminothiolane) plus neutron scattering positioning in the 30S subunit

    PMID:2437527 PMID:2437528 PMID:3005967 PMID:3288761

    Open questions at the time
    • Cross-link sites are proximity not atomic contact maps
    • Does not establish causality between contacts and function
  4. 1984 Medium

    Showed the S21–3'-end region undergoes conformational rearrangement during activation, mRNA binding, and subunit joining, framing S21 as a dynamic sensor of initiation state.

    Evidence FRET and fluorescence anisotropy between probes on S21, S1, and the 3' end of 16S rRNA in E. coli 30S subunits

    PMID:6378636 PMID:6378660 PMID:6388639

    Open questions at the time
    • Distance changes are apparent/ensemble measurements
    • Functional consequence of each conformational state not directly tested
  5. 1999 Medium

    Identified a conserved eukaryotic physical partner (LBP/p40, stubarista/Sta) and indicated RPS21 associates loosely with 40S subunits, extending its role beyond bacteria.

    Evidence Drosophila sucrose gradient/polysome analysis with genetic epistasis; human yeast two-hybrid and in vitro binding

    PMID:10022917 PMID:10079194

    Open questions at the time
    • Functional consequence of the RPS21–LBP/p40 interaction not defined
    • Salt-labile association interpretation as initiation factor not structurally confirmed
  6. 2003 High

    Demonstrated that eukaryotic Rps21 is required for 18S rRNA 3'-end maturation and 40S subunit formation, establishing a conserved assembly/processing role parallel to its bacterial function.

    Evidence Gene disruption, sucrose gradient sedimentation, Northern rRNA processing analysis in S. cerevisiae; co-IP and genetics in S. pombe

    PMID:14623272 PMID:14627813

    Open questions at the time
    • Did not resolve the assembly hierarchy or recruited factors
    • Mechanism of 18S 3'-end maturation contribution unspecified
  7. 2023 High

    Defined the structural mechanism of eukaryotic Rps21 in assembly by placing it in the S0-cluster that recruits Nob1 and enables central pseudoknot folding during SSU maturation.

    Evidence Cryo-EM of SSU precursors from S0-cluster expression mutants with 2'-O-methyl modification scoring in yeast

    PMID:36996028

    Open questions at the time
    • Individual contribution of Rps21 versus other S0-cluster members not fully separated
    • Single lab
  8. 2024 Low

    Proposed an extra-ribosomal disease-associated role linking RPS21 to GPX4 stability and tumor cell proliferation, beyond canonical ribosome assembly.

    Evidence Lentiviral knockdown/overexpression, ubiquitination and GPX4 stability assays, and mouse tumor models in hepatocellular carcinoma; siRNA and MAPK readouts in osteosarcoma

    PMID:32612383 PMID:39546956

    Open questions at the time
    • Mechanistic detail of RPS21-driven GPX4 ubiquitination is sparse
    • RPS21–MAPK link not directly dissected
    • Effects may be secondary to general ribosome/translation perturbation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RPS21's ribosome-assembly function relates to its reported extra-ribosomal effects on protein stability and proliferation control remains unresolved.
  • No structure of the mammalian RPS21–LBP/p40 complex
  • No direct demonstration that GPX4/MAPK effects are independent of ribosome assembly
  • No mammalian in vivo loss-of-function assembly data in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0005198 structural molecule activity 3
Localization
GO:0005840 ribosome 3 GO:0005829 cytosol 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-8953854 Metabolism of RNA 2
Partners
LBP/P40NOB1RPS0RPS1RPS11RPS2
Complex memberships
30S ribosomal subunit40S ribosomal subunitS0-cluster

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1981 Ribosomal protein S21 is required for natural mRNA (MS2 RNA and E. coli mRNA) translation initiation but not for poly(U)/poly(A,G,U)-directed translation or AUG-directed fMet-tRNA binding. 30S subunits lacking S21 (by antibody inactivation or reconstitution) fail to bind MS2 RNA at the initiation step. In vitro reconstitution of 30S subunits lacking S21; antibody inactivation; mRNA-dependent initiation complex formation assay European journal of biochemistry High 7028483
1981 Protein S21 is required for the 3' terminus of 16S rRNA to be accessible for intermolecular base-pairing (Shine-Dalgarno interaction). 30S subunits lacking S21 do not bind a complementary deoxyoctanucleotide to the 3' end of 16S RNA and cannot accept MS2 RNA as messenger; addition of S21 to S21-depleted subunits restores both activities. 3'-end labeling of 16S RNA with [32P]pCp; RNase H/oligonucleotide probing; reconstitution of S21-depleted 30S subunits Nucleic acids research High 7232220
1987 E. coli ribosomal protein S21 is cross-linked to 16S rRNA within nucleotides 693–697 (near the 690–720 loop region) and to the 3'-terminal region, establishing direct RNA-protein contact sites in the 30S subunit. Chemical cross-linking with bis-(2-chloroethyl)-methylamine followed by RNA-protein complex isolation and RNA sequencing Nucleic acids research Medium 2437527 2437528
1987 E. coli ribosomal protein S21 is cross-linked to the 3'-terminal dodecanucleotide of 16S rRNA, confirming proximity of S21 to the 3' end of 16S rRNA. Chemical cross-linking with methyl p-azidophenyl acetimidate followed by RNA-protein complex isolation and RNA sequencing Nucleic acids research Medium 2437527
1986 E. coli ribosomal protein S21 is cross-linked to 16S rRNA at positions 723–724 and at the 3' end (positions 1531–1542) by 2-iminothiolane treatment, further defining two distinct contact sites on 16S rRNA. 2-iminothiolane cross-linking with UV irradiation; RNA-protein complex isolation and RNA sequencing Nucleic acids research Medium 3005967
1984 E. coli ribosomal protein S21 binds to 50S ribosomal subunits as well as to 30S subunits, with relative binding affinities 70S > 30S > 50S. The apparent distance between a fluorescent probe on S21 and the 3' end of 16S rRNA increases from ~51 Å to ~61 Å upon addition of 50S subunits to 30S particles. Fluorescence anisotropy; glycerol gradient sedimentation; non-radiative energy transfer (FRET) measurements Biochemistry Medium 6388639
1984 Activation of 30S ribosomal subunits (by heating in 12 mM Mg2+) is associated with movement of the 3' end of 16S rRNA towards ribosomal protein S21, with an apparent distance decrease from 59 Å to 52 Å as measured by FRET. Non-radiative energy transfer (FRET) between fluorescent probes on 3'-end of 16S RNA and cysteine of S21 FEBS letters Medium 6378660
1984 The apparent distances between S21 and the 3' end of 16S rRNA (~5.1 nm) and between S21 and S1 (~6.9 nm) in 30S subunits increase upon binding of poly(U) (mRNA analog) or 50S subunits, indicating conformational rearrangement at the decoding center upon mRNA and subunit association. Non-radiative energy transfer (FRET) with fluorescent probes on S1 cysteine, S21 cysteine, and 3' end of 16S rRNA European journal of biochemistry Medium 6378636
1978 E. coli ribosomal proteins S1, S11, and S21 directly participate in tRNA binding to the 30S ribosome, as unmodified versions of these proteins restore phe-tRNA binding activity to tetranitromethane-inactivated 30S particles. Chemical inactivation of 30S ribosomes with tetranitromethane followed by ribosome reconstitution with individual unmodified proteins; poly(U)-directed phe-tRNA binding assay Nucleic acids research Medium 25421
1999 Drosophila RpS21 (ribosomal protein S21) is bound to native 40S ribosomal subunits in a salt-labile association and is absent from polysomes, suggesting it functions as a translation initiation factor rather than a core ribosomal protein. RpS21 interacts strongly with P40 (encoded by the stubarista/sta gene), a ribosomal peripheral protein. Sucrose gradient sedimentation of native ribosomes; polysome analysis; genetic interaction studies (double mutant analysis) Molecular and cellular biology Medium 10022917
1999 Human 40S ribosomal protein S21 (RPS21) directly binds LBP/p40 (laminin-binding protein precursor p40/ribosome-associated protein), as demonstrated by yeast two-hybrid screening and in vitro binding analysis. The interaction requires a broad, evolutionarily conserved region of LBP/p40. Yeast two-hybrid screening; in vitro binding assay Biochemical and biophysical research communications Medium 10079194
2003 Yeast Rps21 (S. cerevisiae) is required for maturation of the 3' end of 18S rRNA and formation of active 40S ribosomal subunits. Disruption of both RPS21A and RPS21B genes is lethal; single disruptions reduce free 40S subunits, increase free 60S, decrease polysome size, and produce rRNA processing defects identical to those of Rps0 mutants. Gene disruption; sucrose gradient sedimentation; rRNA processing analysis by Northern blotting; tetrad dissection Nucleic acids research High 14627813
2003 Fission yeast (S. pombe) Rps0p physically associates with Rps21 protein; both genes are essential, and loss of either causes deficiency of 40S ribosomal subunit formation linked to insufficient 18S rRNA stability. Co-immunoprecipitation (Rps0 binding protein identification); tetrad dissection; inducible rescue strains; 40S subunit analysis Biochemical and biophysical research communications Medium 14623272
2023 In yeast, rpS21/eS21 (together with rpS0/uS2 and rpS2/uS5 as the S0-cluster) is required for the initial recruitment of the pre-rRNA processing factor Nob1 and for final maturation of the central pseudoknot of 18S rRNA. Cryo-EM of S0-cluster expression mutants revealed hierarchical rRNA folding defects in cytoplasmic SSU precursors. Cryo-EM structural analysis of SSU precursors from rpS21/eS21 expression mutant yeast strains; unbiased 2'-O-methyl modification scoring PloS one High 36996028
2024 RPS21 modulates the ubiquitination and stability of GPX4 in hepatocellular carcinoma cells. Knockdown or overexpression of RPS21 significantly altered HCC cell proliferation and migration in cell lines and mouse tumor models. Lentiviral knockdown and overexpression; ubiquitination assay; GPX4 protein stability assay; mouse tumor models Translational oncology Low 39546956
2020 Knockdown of RPS21 in osteosarcoma cell lines suppresses cell proliferation, migration, and invasion, and inactivates the MAPK signaling pathway as shown by reduced phosphorylation of MAPK pathway proteins. siRNA knockdown; CCK-8 proliferation assay; colony formation; wound-healing and transwell invasion assays; Western blot for MAPK pathway proteins Cancer management and research Low 32612383
1988 Ribosomal protein S21 of the E. coli 30S subunit is positioned by neutron scattering, completing the mapping of all 30S proteins. Its position is consistent with proximity to the 3' end of 16S rRNA. Neutron scattering distance measurements of protein pairs in the 30S subunit Journal of molecular biology Medium 3288761

Source papers

Stage 0 corpus · 57 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1983 The operon that encodes the sigma subunit of RNA polymerase also encodes ribosomal protein S21 and DNA primase in E. coli K12. Cell 237 6186393
1988 Interaction of ribosomal proteins S5, S6, S11, S12, S18 and S21 with 16 S rRNA. Journal of molecular biology 94 2459389
1988 Positions of S2, S13, S16, S17, S19 and S21 in the 30 S ribosomal subunit of Escherichia coli. Journal of molecular biology 88 3288761
1981 Basepairing potential of the 3' terminus of 16S RNA: dependence on the functional state of the 30S subunit and the presence of protein S21. Nucleic acids research 81 7232220
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
2009 M-CSF elevates c-Fos and phospho-C/EBPalpha(S21) via ERK whereas G-CSF stimulates SHP2 phosphorylation in marrow progenitors to contribute to myeloid lineage specification. Blood 55 19587381
1987 RNA-protein cross-linking in Escherichia coli 30S ribosomal subunits; determination of sites on 16S RNA that are cross-linked to proteins S3, S4, S7, S9, S10, S11, S17, S18 and S21 by treatment with bis-(2-chloroethyl)-methylamine. Nucleic acids research 54 2437528
1987 RNA-protein cross-linking in Escherichia coli 30S ribosomal subunits; determination of sites on 16S RNA that are cross-linked to proteins S3, S4, S5, S7, S8, S9, S11, S13, S19 and S21 by treatment with methyl p-azidophenyl acetimidate. Nucleic acids research 53 2437527
1981 The function of ribosomal protein S21 in protein synthesis. European journal of biochemistry 52 7028483
1999 Down-regulation of RpS21, a putative translation initiation factor interacting with P40, produces viable minute imagos and larval lethality with overgrown hematopoietic organs and imaginal discs. Molecular and cellular biology 47 10022917
2010 Mutational analysis of the S21 pinholin. Molecular microbiology 44 20132441
1994 A cold-regulated cyanobacterial gene cluster encodes RNA-binding protein and ribosomal protein S21. Plant molecular biology 42 8193307
1975 Determination of the complete amino acid sequence of protein S21 from Escherichia coli ribosomes. Hoppe-Seyler's Zeitschrift fur physiologische Chemie 38 765257
2015 Diversity of acid stress resistant variants of Listeria monocytogenes and the potential role of ribosomal protein S21 encoded by rpsU. Frontiers in microbiology 35 26005439
2003 Ribosomal proteins Rps0 and Rps21 of Saccharomyces cerevisiae have overlapping functions in the maturation of the 3' end of 18S rRNA. Nucleic acids research 35 14627813
1986 RNA-protein cross-linking in Escherichia coli ribosomal subunits: localization of sites on 16S RNA which are cross-linked to proteins S17 and S21 by treatment with 2-iminothiolane. Nucleic acids research 33 3005967
1984 Binding of S21 to the 50S subunit and the effect of the 50S subunit on nonradiative energy transfer between the 3' end of 16S RNA and S21. Biochemistry 31 6388639
2022 MYPT1/PP1-Mediated EZH2 Dephosphorylation at S21 Promotes Epithelial-Mesenchymal Transition in Fibrosis through Control of Multiple Families of Genes. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 27 35293697
2014 Cell motility and biofilm formation in Bacillus subtilis are affected by the ribosomal proteins, S11 and S21. Bioscience, biotechnology, and biochemistry 27 25035996
2010 Mapping the pinhole formation pathway of S21. Molecular microbiology 25 20815821
1997 Temperature-dependent regulation of the ribosomal small-subunit protein S21 in the cyanobacterium Anabaena variabilis M3. Journal of bacteriology 25 9371454
2019 Metabolism of 17β-estradiol by Novosphingobium sp. ES2-1 as probed via HRMS combined with 13C3-labeling. Journal of hazardous materials 21 31862352
1980 The gene for ribosomal protein S21, rpsU, maps close to dnaG at 66.5 min on the Escherichia coli chromosomal linkage map. Journal of bacteriology 20 7000750
2022 Phage-encoded ribosomal protein S21 expression is linked to late-stage phage replication. ISME communications 18 37938675
2012 Association between S21 substitution in the core protein of hepatitis B virus and fulminant hepatitis. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 17 22795596
1978 Evidence that proteins S1, S11 and S21 directly participates in the binding of transfer RNA to the 30S ribosome. Nucleic acids research 17 25421
2021 Pinholin S21 mutations induce structural topology and conformational changes. Biochimica et biophysica acta. Biomembranes 15 34499883
2020 Down-Regulation of Ribosomal Protein RPS21 Inhibits Invasive Behavior of Osteosarcoma Cells Through the Inactivation of MAPK Pathway. Cancer management and research 15 32612383
1999 Ribosome-associated protein LBP/p40 binds to S21 protein of 40S ribosome: analysis using a yeast two-hybrid system. Biochemical and biophysical research communications 15 10079194
2020 Structural Dynamics and Topology of the Inactive Form of S21 Holin in a Lipid Bilayer Using Continuous-Wave Electron Paramagnetic Resonance Spectroscopy. The journal of physical chemistry. B 14 32501696
2017 Morphology, topology and dimensions of the heart and arteries of genetically normal and mutant mouse embryos at stages S21-S23. Journal of anatomy 14 28776665
1984 The distance between S1, S21, and the 3' end of 16S RNA in 30S ribosomal subunits. The effect of poly(uridylic acid) and 50S subunits on these distances. European journal of biochemistry 14 6378636
2014 Highly efficient transformation of Stenotrophomonas maltophilia S21, an environmental isolate from soil, by electroporation. Journal of microbiological methods 13 25300664
2008 Pistil-function breakdown in a new S-allele of European pear, S21*, confers self-compatibility. Plant cell reports 13 19096853
2020 Conformational Differences Are Observed for the Active and Inactive Forms of Pinholin S21 Using DEER Spectroscopy. The journal of physical chemistry. B 11 33289567
1992 Structural determination of Saccharomyces cerevisiae rig gene and identification of its product as ribosomal protein S21. FEBS letters 11 1644188
2018 Solid phase synthesis and spectroscopic characterization of the active and inactive forms of bacteriophage S21 pinholin protein. Analytical biochemistry 9 30528914
2003 Ribosomal proteins S0 and S21 are involved in the stability of 18S rRNA in fission yeast, Schizosaccharomyces pombe. Biochemical and biophysical research communications 9 14623272
2017 Expression and comparative characterization of complete and C-terminally truncated forms of saccharifying α-amylase from Lactobacillus plantarum S21. International journal of biological macromolecules 8 28587961
2004 Cloning, characterization, and developmental expression of the ribosomal protein S21 gene of the Mediterranean fruit fly Ceratitis capitata. Archives of insect biochemistry and physiology 8 15211551
1991 The amino-acid sequences of the Bacillus stearothermophilus ribosomal proteins S17 and S21 and their comparison to homologous proteins of other ribosomes. Biological chemistry Hoppe-Seyler 8 1772592
2012 DISCRIMINATION OF Burkholderia mallei/pseudomallei FROM Burkholderia thailandensis BY SEQUENCE COMPARISON OF A FRAGMENT OF THE RIBOSOMAL PROTEIN S21 (RPSU) GENE. European journal of microbiology & immunology 7 23227305
1984 Movement of the 3'-end of 16 S RNA towards S21 during activation of 30 S ribosomal subunits. FEBS letters 7 6378660
2024 Fe(III)-Aided Novosphingobium sp. ES2-1 Regulates Molecular Mechanisms of 17β-Estradiol Biodegradation. Environmental science & technology 6 39636603
2024 RPS21 Enhances hepatocellular carcinoma development through GPX4 stabilization. Translational oncology 4 39546956
2022 Allele-specific alternative splicing of Drosophila Ribosomal protein S21 suppresses a lethal mutation in the Phosphorylated adaptor for RNA export (Phax) gene. G3 (Bethesda, Md.) 4 35920767
2021 Probing the local secondary structure of bacteriophage S21 pinholin membrane protein using electron spin echo envelope modulation spectroscopy. Biochimica et biophysica acta. Biomembranes 4 34906602
1995 The primary structures of rat ribosomal proteins: the characterization of the cDNAs for S21 and L39, corrections in the sequences of L7 and L18a, and the identification of L33. Biochemical and biophysical research communications 4 7654221
2004 [Precursors of HLDF differentiation factor and ribosomal protein RPS21 have a common N-terminal sequence]. Bioorganicheskaia khimiia 3 15143667
2023 Impact of the yeast S0/uS2-cluster ribosomal protein rpS21/eS21 on rRNA folding and the architecture of small ribosomal subunit precursors. PloS one 2 36996028
2000 [Cloning and characterization of the human ribosomal protein S21 gene []. Bioorganicheskaia khimiia 2 10900511
2020 Biochemical and computational study of an alginate lyase produced by Pseudomonas aeruginosa strain S21. Iranian journal of basic medical sciences 1 32489560
2019 Identification of evolutionary conserved DNA sequence and corresponding S21 ribosomal protein region for diagnostic purposes of all Borrelia spirochetes. Acta biochimica Polonica 1 30630189
2022 Draft Genome Sequence of Lysinibacillus sp. Strain BPa_S21, Isolated from Petroleum-Contaminated Soil in Delta State, Nigeria. Microbiology resource announcements 0 35861537
2017 Complete genome sequence of a natural compounds producer, Streptomyces violaceus S21. Genomics data 0 28491497
2004 [Comparison of fetal ECG recordings using STAN S21 analyser and external ECG of newborns, in relation to enzymatic ischaemic markers and acid-base parameters in umbilical blood]. Ginekologia polska 0 15754570
1990 New TaqI allele detected by X-chromosome probe s21 (DXS17). Nucleic acids research 0 1971941

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