Affinage

RPS19

Small ribosomal subunit protein eS19 · UniProt P39019

Length
145 aa
Mass
16.1 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPS19 is a structural protein of the small (40S) ribosomal subunit that is required for a specific step in 18S rRNA maturation and pre-40S particle assembly (PMID:16159874, PMID:17376718). It localizes principally to the nucleolus through two defined nucleolar localization signals (N-terminal Met1–Arg16 and C-terminal Gly120–Asn142), and DBA-associated point mutations that disrupt either signal cause mislocalization and protein destabilization (PMID:12586610). Structurally it forms a five α-helix bundle in which DBA missense mutations either disrupt folding (class I) or alter surface basic patches needed for incorporation into pre-40S particles (class II) (PMID:17726054). Depletion of RPS19 blocks 3′-end processing of 18S rRNA, traps aberrant pre-40S particles lacking late maturation factors, and reduces 40S subunit and 80S ribosome levels; the same processing defect is seen in cells from DBA patients (PMID:16159874, PMID:17376718, PMID:16990592). Beyond processing, RPS19 loss also lowers RNA polymerase I activity and its occupancy at rRNA genes, reducing rRNA synthesis (PMID:27734913). Heterozygous loss is the disease mechanism in Diamond-Blackfan anemia, an erythroid-selective bone marrow failure: RPS19 was identified as the causal gene mutated in ~25% of DBA patients, with nonsense/nonstop alleles degraded by NMD/nonstop decay and unstable mutant proteins cleared by the proteasome to produce haploinsufficiency, while the R62W allele acts as a dominant negative (PMID:9988267, PMID:15523650, PMID:18768533, PMID:20606162). RPS19 deficiency impairs erythropoiesis and exhausts hematopoietic stem cells, acting upstream of p53 to drive G1 arrest and, in non-erythroid cells, p53-dependent TNF-α that activates p38 MAPK and suppresses GATA1 in erythroid progenitors (PMID:15626736, PMID:21989989, PMID:36413407, PMID:25270909, PMID:17962699). Independently of its ribosomal role, extracellular RPS19 has immune-modulatory activity: a crosslinked homodimer engages the C5a receptor through two defined binding sites to recruit monocytes/MDSCs and inhibit neutrophil migration, it binds and inhibits MIF, and it is co-opted by hantavirus nucleocapsid protein at the 40S head to drive viral translation initiation (PMID:11733378, PMID:28228558, PMID:19155217, PMID:20844026, PMID:21296889).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 High

    Established RPS19 as a disease gene by identifying heterozygous loss-of-function and missense mutations in Diamond-Blackfan anemia, converting an uncharacterized 19q13 locus into a defined causal entity.

    Evidence Translocation breakpoint cloning and direct sequencing in 40 unrelated DBA patients

    PMID:9988267

    Open questions at the time
    • Did not define the molecular function of RPS19
    • Did not explain why erythropoiesis is selectively affected
  2. 2003 High

    Defined where RPS19 acts in the cell and how DBA mutations disrupt it, mapping two nucleolar localization signals whose loss mislocalizes and destabilizes the protein.

    Evidence GFP-fusion deletion mapping and immunofluorescence in Cos-7 cells with DBA mutants

    PMID:12586610

    Open questions at the time
    • Did not establish the biochemical step requiring nucleolar RPS19
    • Mechanism of protein destabilization not defined
  3. 2005 High

    Pinpointed RPS19's molecular function as 18S rRNA 3′-end maturation and pre-40S assembly, and showed DBA missense mutations recapitulate the processing defect in vivo.

    Evidence Yeast Rps19 deletion, pre-rRNA processing analysis, pre-ribosome affinity purification, and DBA-mutant mutagenesis

    PMID:16159874

    Open questions at the time
    • Did not extend processing role to human hematopoietic cells at the time
    • Link between processing failure and erythroid specificity unresolved
  4. 2006 High

    Confirmed the rRNA-processing role in human hematopoietic cells and patient cells, bridging the yeast mechanism to DBA.

    Evidence siRNA knockdown in TF-1 cells and pre-rRNA analysis in DBA patient CD34- bone marrow cells

    PMID:16990592

    Open questions at the time
    • Did not connect processing defect to a downstream death/arrest pathway
    • Erythroid selectivity not explained
  5. 2007 High

    Provided a structural and quantitative framework, defining the helix-bundle fold and classifying DBA mutations as folding-defective vs. incorporation-defective, and showing the magnitude of 40S/80S loss upon depletion.

    Evidence X-ray crystallography of archaeal RPS19 with yeast complementation; siRNA depletion with sucrose-gradient and Northern analysis in HeLa/U-2 OS

    PMID:17376718 PMID:17726054

    Open questions at the time
    • Structure was of archaeal ortholog, not human within ribosome context
    • Did not resolve why specific residues form basic incorporation patches
  6. 2004 High

    Demonstrated a specific, dose-dependent requirement for RPS19 in human erythropoiesis and showed null lethality with viable heterozygotes, supporting haploinsufficiency as the DBA mechanism.

    Evidence Lentiviral siRNA knockdown with rescue in primary CD34+ cells; targeted Rps19 knockout in mice

    PMID:15082795 PMID:15626736

    Open questions at the time
    • Mouse heterozygotes lacked an overt DBA phenotype
    • Did not identify the signaling pathway downstream of deficiency
  7. 2004 Medium

    Explained how mutant alleles lower RPS19 levels at the mRNA stage, showing nonsense/nonstop mutations trigger translation-dependent NMD and nonstop decay.

    Evidence RT-PCR/Northern of DBA patient lymphoblasts and fibroblasts with translation inhibition

    PMID:15523650

    Open questions at the time
    • Single-lab patient-cell study
    • Did not quantify contribution of NMD vs. protein-level mechanisms to overall haploinsufficiency
  8. 2008 High

    Placed RPS19 deficiency upstream of the p53 (and ΔNp63) stress pathway in a vertebrate model and showed this is a shared response across ribosomal protein genes.

    Evidence Zebrafish morpholino knockdown with p53/ΔNp63 co-suppression epistasis and comparison to other RP knockdowns

    PMID:18515656 PMID:18653748

    Open questions at the time
    • Did not explain erythroid selectivity within the p53 response
    • ΔNp63 role outside zebrafish unaddressed
  9. 2008 Medium

    Identified proteasomal degradation as a mechanism clearing unstable mutant RPS19, completing the protein-level arm of haploinsufficiency.

    Evidence GFP-RPS19 mutant panel in Cos-7 cells with lactacystin/MG132/bortezomib rescue of expression and localization

    PMID:18768533

    Open questions at the time
    • E3 ligase and degron not identified
    • Single-lab overexpression system
  10. 2009 Medium

    Defined the cell-cycle consequence of RPS19 loss as a p21/p27-associated G1 arrest with reduced Cyclin-E/CDK2/Rb, distinguishing it from RPS24 deficiency and identifying the proliferative erythroid stage as most sensitive.

    Evidence siRNA knockdown in TF-1 cells and primary DBA fibroblasts with flow cytometry and cell-cycle protein blots

    PMID:17962699 PMID:19689926

    Open questions at the time
    • Single-lab studies
    • Did not connect cell-cycle markers to the p53 stress axis mechanistically
  11. 2010 High

    Formally tested a dominant-negative mechanism in vivo, showing the R62W allele causes anemia and impaired terminal erythroid maturation with transcriptomic overlap to patients.

    Evidence Constitutive and conditional RPS19R62W transgenic mice with hematology and RNA profiling

    PMID:20606162

    Open questions at the time
    • Did not define how R62W interferes with wild-type RPS19 biochemically
    • Relative contribution of dominant-negative vs. haploinsufficient alleles in patients unresolved
  12. 2011 High

    Modeled graded RPS19 loss in vivo, demonstrating HSC exhaustion and lethal marrow failure rescued by gene transfer or p53 loss, while separately showing the erythroid defect has a p53-independent component.

    Evidence Inducible transgenic RNAi mouse with p53-knockout epistasis and lentiviral rescue; zebrafish RPS19/tp53 co-knockdown

    PMID:21223253 PMID:21989989

    Open questions at the time
    • Identity of the p53-independent erythroid pathway not defined
    • How a general defect produces lineage-selective failure unresolved
  13. 2014 High

    Resolved part of the p53-dependent erythroid mechanism by showing non-erythroid p53-driven TNF-α activates p38 MAPK to suppress GATA1 in erythroid cells, providing a non-cell-autonomous route to anemia.

    Evidence siRNA knockdown cell culture with TNF-α ELISA, p38 inhibition, and etanercept/p53 epistasis in zebrafish

    PMID:25270909

    Open questions at the time
    • Source and trigger of TNF-α induction not fully defined
    • Relationship to the p53-independent erythroid pathway unclear
  14. 2016 Medium

    Extended RPS19's role beyond rRNA processing to rRNA synthesis, showing depletion reduces RNA Pol I activity and occupancy at rDNA.

    Evidence siRNA knockdown with nuclear run-on, Pol I ChIP, and DBA patient RT-qPCR

    PMID:27734913

    Open questions at the time
    • Mechanism linking RPS19 loss to Pol I downregulation only partially defined (CDK2/AKT/AMPK)
    • Single-lab study
  15. 2023 High

    Provided a definitive human model of haploinsufficiency, showing CRISPR RPS19+/- HSPCs have an erythroid and HSC repopulation defect corrected by gene transfer or TP53 disruption.

    Evidence CRISPR editing of primary human CD34+ HSPCs with xenotransplantation, TP53 epistasis, and lentiviral rescue

    PMID:36413407

    Open questions at the time
    • Did not isolate the p53-independent erythroid component in human cells
    • Molecular link from ribosome deficit to HSC self-renewal loss not fully defined
  16. 2001 High

    Revealed an extraribosomal function, mapping two C5a-receptor-binding sites on the crosslinked RPS19 homodimer that recruit monocytes and inhibit neutrophil migration.

    Evidence Site-directed mutagenesis of recombinant RPS19 and synthetic peptides in monocyte/neutrophil chemotaxis assays

    PMID:11733378

    Open questions at the time
    • Physiological source and crosslinking mechanism in vivo not fully defined
    • Relationship to ribosomal pool unclear
  17. 2009 High

    Identified RPS19 as a negative regulator of MIF, binding it directly and blocking MIF–CD74 engagement and MIF-driven monocyte adhesion.

    Evidence Endogenous co-IP, surface plasmon resonance (KD ~1.3 µM), MIF pulldowns, and monocyte adhesion under flow

    PMID:19155217

    Open questions at the time
    • In vivo relevance of MIF inhibition not established
    • Structural basis of RPS19–MIF interaction undefined
  18. 2017 Medium

    Connected the extracellular C5aR activity to tumor immunity, showing apoptotic-cell-released RPS19 recruits MDSCs via C5aR1 to suppress anti-tumor T-cell responses.

    Evidence Binding and MDSC functional assays, tumor-cell RPS19 knockdown, C5aR1 blockade, and a transgenic breast cancer mouse model

    PMID:28228558

    Open questions at the time
    • Single-lab study
    • Contribution relative to canonical C5a in tumors not quantified
  19. 2010 High

    Showed RPS19 is hijacked by hantavirus nucleocapsid protein at the 40S head to enable viral mRNA translation initiation, defining a host-factor role.

    Evidence Co-IP, isothermal titration calorimetry, in vitro and cell-based translation assays; later deletion/CD/sedimentation mapping of the N-protein interaction domain

    PMID:20844026 PMID:21296889 PMID:25062117

    Open questions at the time
    • Whether this targets ribosomal or free RPS19 not resolved
    • Generalizability to other viruses unaddressed
  20. 2005 Medium

    Linked RPS19 to kinase signaling and a candidate partner, identifying PIM-1-mediated phosphorylation and the nucleolar protein S19BP as interactors.

    Evidence Yeast two-hybrid screens, Co-IP, and in vitro kinase assays; immunolocalization of S19BP

    PMID:16266891 PMID:16289379

    Open questions at the time
    • Functional consequence of PIM-1 phosphorylation not established
    • S19BP interaction is a single Y2H with no reciprocal validation or function
  21. 2009 High

    Identified a specific regulatory phosphorylation, showing CaM kinase Iα phosphorylates RPS19 at Ser59 and that phospho-RPS19 is present in 80S ribosomes and enhances S19BP binding.

    Evidence In vitro kinase assays across CaMK isoforms, Ser59Ala mutagenesis, phospho-specific antibody, and fractionation

    PMID:19200342

    Open questions at the time
    • In vivo functional role of Ser59 phosphorylation unresolved
    • Connection to ribosome biogenesis or DBA not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular identity of the p53-independent, RPS19-dependent pathway driving erythroid-selective failure, and how a general ribosome-biogenesis deficit is translated into lineage selectivity and HSC exhaustion, remains unresolved.
  • No defined effector for the p53-independent erythroid defect identified in human cells
  • Mechanism converting ribosomal stress into erythroid specificity unknown
  • Relationship between extraribosomal C5aR/MIF functions and DBA pathology untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0003723 RNA binding 2 GO:0048018 receptor ligand activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005840 ribosome 3 GO:0005576 extracellular region 2 GO:0005730 nucleolus 2
Pathway
R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 2 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
C5AR1CAMK1MIFPIM1S19BP
Complex memberships
40S ribosomal small subunitpre-40S ribosomal particle

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 RPS19 is mutated (nonsense, frameshift, splice site, missense mutations, and intragenic deletions) in approximately 25% of Diamond-Blackfan anemia (DBA) patients; the gene was cloned from a chromosome 19q13 translocation breakpoint, establishing RPS19 as the causal gene for a subset of DBA cases. Chromosomal translocation breakpoint cloning; direct sequencing of RPS19 in 40 unrelated DBA patients Nature genetics High 9988267
2006 Human RPS19 is required for a specific step in the maturation of 40S ribosomal subunits; siRNA-mediated depletion of RPS19 in TF-1 cells blocks pre-rRNA processing, and CD34- bone marrow cells from DBA patients with RPS19 mutations show the same processing defect. siRNA knockdown in hematopoietic cell line TF-1; pre-rRNA processing intermediate analysis; primary DBA patient CD34- cells Blood High 16990592
2005 Yeast Rps19 is strictly required for maturation of the 3′-end of 18S rRNA and for assembly/maturation of pre-40S particles; depletion causes nuclear retention of aberrant pre-40S particles lacking late-maturation factors (Enp1, Tsr1, Rio2). DBA patient-associated missense mutations introduced into yeast Rps19 recapitulate the pre-rRNA processing defects, directly linking these mutations to ribosome biogenesis failure. Yeast Rps19 gene deletion; pre-rRNA processing analysis; affinity purification of pre-ribosomal particles; site-directed mutagenesis introducing DBA-associated amino acid substitutions The Journal of biological chemistry High 16159874
2007 Crystal structure of archaeal RPS19 (Pyrococcus abyssi) reveals a five α-helix bundle organized around a central amphipathic α-helix corresponding to the DBA mutation hotspot. DBA missense mutations were classified as class I (disrupting protein folding) or class II (altering surface basic patches required for incorporation into pre-40S ribosomal particles). In vivo yeast analysis confirmed that class II residues are essential for incorporation into pre-ribosomes. X-ray crystallography; in vivo yeast complementation with structure-guided mutants Nucleic acids research High 17726054
2007 siRNA-mediated depletion of RPS19 in HeLa and U-2 OS cells causes a dramatic reduction in 40S ribosomal subunits and mature 80S ribosomes, an excess of free 60S subunits, accumulation of 21S and 20S pre-rRNA intermediates, and post-transcriptional reduction in RPS6 and RPS16 levels (but not RPL7 or RPL26), indicating RPS19 is required for specific steps in 18S rRNA processing. siRNA knockdown; sucrose-gradient sedimentation; Northern blot for rRNA processing intermediates; Western blot for ribosomal proteins Blood cells, molecules & diseases High 17376718
2003 RPS19 localizes primarily to the nucleolus, where it co-localizes with nucleolin. Two nucleolar localization signals (NoLS) were identified: amino acids Met1–Arg16 (N-terminal) and Gly120–Asn142 (C-terminal). DBA-associated mutations Val15Phe and Gly127Gln each disrupted one NoLS, causing mislocalization of RPS19 away from the nucleolus and dramatically decreased mutant protein expression. GFP fusion constructs; N- and C-terminal deletion analysis; immunofluorescence in Cos-7 cells; Western blot Blood High 12586610
2004 RPS19 deficiency (via siRNA lentiviral knockdown) in human CD34+ cord blood and bone marrow cells causes impaired erythroid colony formation, reduced proliferative capacity, and a block in erythroid differentiation correlated with the degree of RPS19 knockdown; the phenotype was rescued by an siRNA-resistant RPS19 transcript, establishing a specific requirement for RPS19 in erythropoiesis. Lentiviral siRNA knockdown in primary CD34+ cells; erythroid colony assays (CFU-E); liquid erythroid differentiation cultures; rescue with siRNA-resistant RPS19 cDNA Blood High 15626736
2004 Homozygous disruption of murine Rps19 is lethal prior to blastocyst formation, indicating RPS19 is essential for early embryonic development; heterozygous mice have normal growth and hematopoiesis, consistent with haploinsufficiency as the disease mechanism in DBA. Targeted gene disruption (knockout) in C57BL/6J mice; blastocyst-stage genotyping Molecular and cellular biology High 15082795
2008 rps19 deficiency in zebrafish leads to hematopoietic and developmental abnormalities (resembling DBA) mediated by dysregulation of p53 and deltaNp63; during gastrulation, induced deltaNp63 in erythroid progenitors contributes to blood defects, and suppression of p53 and deltaNp63 alleviates rps19-deficient phenotypes. Other RP deficiencies (S8, S11, S18) similarly activate the p53 pathway. Morpholino knockdown in zebrafish; genetic epistasis (p53 and deltaNp63 co-suppression); phenotypic rescue assays Blood High 18515656
2009 RPS19 directly binds macrophage migration inhibitory factor (MIF) with a KD of ~1.3 µM; this interaction inhibits MIF binding to its receptor CD74, and RPS19 significantly reduces CXCR2-dependent MIF-triggered monocyte adhesion to endothelial cells, establishing RPS19 as an extracellular negative regulator of MIF pro-inflammatory function. In vivo biotin-tagging; endogenous co-immunoprecipitation; surface plasmon resonance; pulldown with wild-type and mutant MIF; monocyte adhesion assay under flow conditions The Journal of biological chemistry High 19155217
2001 The crosslinked RPS19 homodimer attracts monocytes and inhibits neutrophil migration via the C5a receptor (C5aR). Using site-directed mutants and synthetic peptides, two receptor-binding sites were identified on the RPS19 dimer: a basic cluster region (Lys41-His42-Lys43) as the first binding site (high-affinity anchor) and Leu131-Asp132-Arg133 as the second site (triggering chemotaxis), mirroring the two-step C5a binding mechanism. Site-directed mutagenesis of recombinant RPS19; synthetic peptides; monocyte/neutrophil chemotaxis assay The American journal of pathology High 11733378
2005 RPS19 interacts with PIM-1 serine-threonine kinase (identified by yeast two-hybrid screening of a fetal liver cDNA library); the interaction was confirmed in vitro and in living cells, and PIM-1 phosphorylates RPS19 in an in vitro kinase assay. Three DBA-associated RPS19 mutations alter PIM-1 binding, linking erythropoietic growth factor signaling to RPS19. Yeast two-hybrid screen; in vitro binding; co-immunoprecipitation in 293T cells; in vitro kinase assay Haematologica Medium 16266891
2009 CaM kinase Iα (but not Iβ1, Iβ2, II, or IV) phosphorylates RPS19 at Ser59 in vitro; mutagenesis confirmed Ser59 as the primary phosphorylation site. Phospho-Ser59 RPS19 is present in 80S ribosomes in rat brain, and CaM kinase Iα-mediated phosphorylation augments the interaction of RPS19 with S19-binding protein (S19BP). In vitro kinase assay with multiple CaM kinase isoforms; site-directed mutagenesis (Ser59Ala); phospho-specific antibody; subcellular fractionation; KN93 inhibitor in GT1-7 cells Journal of neurochemistry High 19200342
2004 Nonsense and nonstop mutations in the RPS19 gene trigger nonsense-mediated decay (NMD) and nonstop decay of mutant RPS19 mRNA, respectively, reducing steady-state mRNA levels and contributing to RPS19 haploinsufficiency in DBA. Translation inhibition stabilized the mutated transcripts, confirming the degradation is translation-dependent. RT-PCR and Northern blot analysis of lymphoblastoid cells and fibroblasts from DBA patients; translation inhibitor experiments Human mutation Medium 15523650
2010 The RPS19 R62W missense mutation acts as a dominant negative: constitutive expression of RPS19R62W in transgenic mice was lethal, and conditional expression caused growth retardation, mild anemia with reduced erythroid progenitors, and significant inhibition of terminal erythroid maturation, with >700 dysregulated genes overlapping DBA patient RNA profiles. Transgenic mouse model (constitutive and conditional RPS19R62W expression); hematological and erythroid progenitor analyses; RNA profiling Blood High 20606162
2011 Inducible, graded transgenic RNAi knockdown of Rps19 in mice causes macrocytic anemia, leukocytopenia, exhaustion of hematopoietic stem cells, and lethal bone marrow failure. Both RPS19 gene transfer and p53 loss rescue the DBA phenotype, placing RPS19 upstream of p53 in a pathway controlling hematopoietic stem cell maintenance. Inducible transgenic RNAi mouse model; hematological analysis; genetic epistasis with p53 knockout; lentiviral RPS19 gene transfer rescue Blood High 21989989
2014 RPS19 deficiency in hematopoietic progenitor cells leads to decreased GATA1 expression in erythroid progenitors and p53-dependent upregulation of TNF-α in non-erythroid cells. TNF-α activates p38 MAPK in erythroid cells, causing reduced GATA1 expression; inhibition of TNF-α (by etanercept) or p53 rescued the anemia phenotype in rps19-deficient zebrafish. Cell culture with siRNA knockdown; Western blot; ELISA for TNF-α; p38 MAPK inhibition; genetic epistasis in zebrafish (etanercept treatment) Blood High 25270909
2008 RPS19 deficiency in zebrafish (morpholino knockdown) causes severe reduction in blood cells and craniofacial/tail deformities during early embryogenesis; rescue by wild-type rps19 mRNA but not by DBA patient-derived mutant rps19 mRNAs establishes that DBA-associated mutations impair RPS19 function essential for hematopoietic differentiation. Morpholino antisense knockdown in zebrafish; mRNA rescue with wild-type vs. DBA-mutant rps19; comparative phenotype analysis with rpl35, rpl35a, rplp2 knockdowns Human molecular genetics High 18653748
2010 Hantavirus nucleocapsid protein (N) specifically interacts with RPS19 at the head region of the 40S ribosomal subunit, and this N-RPS19 interaction is required for N-mediated translation initiation of viral mRNAs; characterized as a 1:1 enthalpy-driven interaction with high affinity, and RPS19 undergoes a conformational change upon binding N. Co-immunoprecipitation; isothermal titration calorimetry; in vitro translation assay in rabbit reticulocyte lysates and in cells; binding stoichiometry analysis Journal of virology / The Journal of biological chemistry High 20844026 21296889
2014 The N-RPS19 interaction domain maps to the N-terminus of hantavirus N protein; deletion of this domain does not affect N secondary structure but alters trimer conformation. The N-RPS19 interaction facilitates ribosome loading by enabling N molecules bound to the mRNA 5′ cap and to RPS19 of the 40S subunit to undergo N-N interaction. Deletion mutagenesis; circular dichroism; sedimentation analysis; in vitro translation assays The Biochemical journal Medium 25062117
2016 RPS19 depletion causes a reduction in RNA Polymerase I (Pol I) activity and decreased association of Pol I with rRNA genes (assessed by nuclear run-on and ChIP), leading to reduced rRNA synthesis—distinct from and in addition to pre-rRNA processing defects. Phosphorylation of CDK2, AKT, and AMPK is altered during ribosomal stress and may mediate Pol I downregulation. DBA patient cells show reduced 47S precursor levels. siRNA knockdown of RPS19 (and RPS6, RPL11); nuclear run-on assay; chromatin immunoprecipitation (ChIP) for Pol I; RT-qPCR in DBA patient RNA Scientific reports Medium 27734913
2008 Proteasomal degradation is a key pathway regulating expression and nucleolar localization of unstable DBA-associated RPS19 mutant proteins; treatment with proteasome inhibitors (lactacystin, MG132, bortezomib) restored expression levels and normal nucleolar localization of several unstable mutant RPS19 proteins. GFP-RPS19 mutant transfection in Cos-7 cells; Western blot with anti-RPS19 antibody; immunofluorescence; proteasome inhibitor treatment Haematologica Medium 18768533
2017 RPS19 is released from apoptotic tumor cells and interacts with complement C5a receptor 1 (C5aR1) on tumor-infiltrating myeloid-derived suppressor cells (MDSCs), promoting their recruitment to tumors, inducing TGF-β production, skewing T cell responses to Th2, generating regulatory T cells, and reducing CD8+ T cell infiltration. Reducing RPS19 in tumor cells or blocking RPS19–C5aR1 interaction impairs tumor growth. Cell-based binding assays; tumor immunology assays; MDSC functional assays; RPS19 knockdown in tumor cells; C5aR1 blocking; transgenic breast cancer mouse model Journal of immunology Medium 28228558
2009 RPS19-deficient TF-1 cells show G0/G1 cell cycle arrest associated with accumulation of p21 and p27, decreased Cyclin-E and CDK2, decreased Rb, increased apoptosis with altered Bcl-2/Bax/Bad levels; RPS19 silencing blocks EPO-induced development of erythroid progenitors but does not affect cells already committed to the erythroid lineage (GPA-positive cells), defining the proliferative stage as most sensitive. siRNA knockdown in TF-1 cells; flow cytometry (cell cycle, Annexin V); Western blot for cell cycle and apoptosis proteins; erythroid differentiation assay Stem cells Medium 17962699
2009 RPS19-deficient primary fibroblasts from DBA patients accumulate in G1 phase with reduced levels of Cyclin-E, CDK2, and Rb protein, whereas RPS24-deficient fibroblasts show S-phase delay with increased p21 and Cyclin-E/CDK4/CDK6, demonstrating that RPS19 and RPS24 insufficiency cause distinct cell cycle defects. Primary DBA patient fibroblasts; flow cytometry; Western blot for cell cycle regulators Biochimica et biophysica acta Medium 19689926
2005 A novel nucleolar protein, S19BP (S19-binding protein), was identified as an RPS19-interacting partner by yeast two-hybrid screening; immunolocalization showed S19BP is concentrated in nucleoli. Yeast two-hybrid screening of mouse RPS19 against cDNA library; immunofluorescence in Cos-7 cells Biochemical and biophysical research communications Low 16289379
2023 CRISPR/Cas9-generated RPS19 haploinsufficiency (RPS19+/-) in human CD34+ HSPCs causes impaired erythropoiesis with normal myelopoiesis in vitro, and profoundly reduced bone marrow repopulation after transplantation into immunodeficient mice (HSC defect). Both defects are partially corrected by RPS19 lentiviral gene transfer or by Cas9 disruption of TP53, placing TP53 downstream of RPS19 haploinsufficiency in the HSC defect. CRISPR/Cas9 genome editing of primary human CD34+ HSPCs; in vitro differentiation; xenotransplantation into immunodeficient mice; genetic epistasis with TP53 disruption; lentiviral RPS19 rescue JCI insight High 36413407
2011 Simultaneous loss-of-function of RPS19 and Tp53 in zebrafish rescued morphological abnormalities but did NOT alleviate erythroid aplasia, establishing that a Tp53-independent but RPS19-dependent pathway is responsible for the erythroid-specific defects in RPS19-deficient zebrafish. Co-injection of RPS19 and tp53 morpholinos in zebrafish; phenotypic analysis of erythroid and morphological defects British journal of haematology Medium 21223253

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nature genetics 662 9988267
1998 Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice. Investigative ophthalmology & visual science 479 9579474
2005 Retinal ganglion cell degeneration is topological but not cell type specific in DBA/2J mice. The Journal of cell biology 329 16247030
2008 Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family. Blood 241 18515656
1999 Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression. Blood 176 10590074
2006 Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits. Blood 156 16990592
2003 Dietary-induced obesity and hypothalamic infertility in female DBA/2J mice. Endocrinology 146 14670988
2004 Targeted disruption of the ribosomal protein S19 gene is lethal prior to implantation. Molecular and cellular biology 134 15082795
2011 Mice with ribosomal protein S19 deficiency develop bone marrow failure and symptoms like patients with Diamond-Blackfan anemia. Blood 117 21989989
2005 Specific Role for Yeast Homologs of the Diamond Blackfan Anemia-associated Rps19 Protein in Ribosome Synthesis. The Journal of biological chemistry 113 16159874
1988 Seizure susceptibility in DBA and C57 mice: the effects of various convulsants. Epilepsia 101 3292231
2007 Cells depleted for RPS19, a protein associated with Diamond Blackfan Anemia, show defects in 18S ribosomal RNA synthesis and small ribosomal subunit production. Blood cells, molecules & diseases 96 17376718
2004 Deficiency of ribosomal protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia. Blood 96 15626736
2008 RPS19 mutations in patients with Diamond-Blackfan anemia. Human mutation 93 18412286
2013 Retinal ganglion cell dendritic atrophy in DBA/2J glaucoma. PloS one 88 23977271
2004 RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anaemia patients with RPS19 mutations. British journal of haematology 88 15384984
2010 A transgenic mouse model demonstrates a dominant negative effect of a point mutation in the RPS19 gene associated with Diamond-Blackfan anemia. Blood 86 20606162
2008 Deficiency of ribosomal protein S19 during early embryogenesis leads to reduction of erythrocytes in a zebrafish model of Diamond-Blackfan anemia. Human molecular genetics 85 18653748
2002 Gene transfer improves erythroid development in ribosomal protein S19-deficient Diamond-Blackfan anemia. Blood 80 12351378
1989 Expression of the DBA/2J Ren-2 gene in the adrenal gland of transgenic mice. The EMBO journal 78 2480233
2005 An RNA interference model of RPS19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray. Blood 75 15755903
2017 The Ribosomal Protein S19 Suppresses Antitumor Immune Responses via the Complement C5a Receptor 1. Journal of immunology (Baltimore, Md. : 1950) 71 28228558
2003 Nucleolar localization of RPS19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 Diamond-Blackfan anemia patients: potential insights into pathophysiology. Blood 71 12586610
2019 Inhibition of monocyte-like cell extravasation protects from neurodegeneration in DBA/2J glaucoma. Molecular neurodegeneration 70 30670050
2009 Abnormal serotonin receptor expression in DBA/2 mice associated with susceptibility to sudden death due to respiratory arrest. Epilepsy research 69 20018491
2012 Primary hematopoietic cells from DBA patients with mutations in RPL11 and RPS19 genes exhibit distinct erythroid phenotype in vitro. Cell death & disease 68 22833095
2012 Cannabinoid CB₂ receptor-mediated regulation of impulsive-like behaviour in DBA/2 mice. British journal of pharmacology 64 21671903
2014 TNF-mediated inflammation represses GATA1 and activates p38 MAP kinase in RPS19-deficient hematopoietic progenitors. Blood 63 25270909
1999 Effects of adenosine receptor agonists and antagonists on audiogenic seizure-sensible DBA/2 mice. European journal of pharmacology 63 10357250
2002 Ribosomal protein S19 expression during erythroid differentiation. Blood 62 12393682
1991 RNA editing makes mistakes in plant mitochondria: editing loses sense in transcripts of a rps19 pseudogene and in creating stop codons in coxI and rps3 mRNAs of Oenothera. Nucleic acids research 57 1762921
2007 Distribution of amyloid precursor protein and amyloid-beta immunoreactivity in DBA/2J glaucomatous mouse retinas. Investigative ophthalmology & visual science 56 17962460
2007 Ribosomal protein S19 deficiency leads to reduced proliferation and increased apoptosis but does not affect terminal erythroid differentiation in a cell line model of Diamond-Blackfan anemia. Stem cells (Dayton, Ohio) 56 17962699
2009 Ribosomal protein S19 interacts with macrophage migration inhibitory factor and attenuates its pro-inflammatory function. The Journal of biological chemistry 55 19155217
2011 Erythropoiesis failure due to RPS19 deficiency is independent of an activated Tp53 response in a zebrafish model of Diamond-Blackfan anaemia. British journal of haematology 54 21223253
2005 Development of cellular models for ribosomal protein S19 (RPS19)-deficient diamond-blackfan anemia using inducible expression of siRNA against RPS19. Molecular therapy : the journal of the American Society of Gene Therapy 52 15771965
2018 Flavonoids Luteolin and Quercetin Inhibit RPS19 and contributes to metastasis of cancer cells through c-Myc reduction. Journal of food and drug analysis 51 29976410
2008 Dependency of intraocular pressure elevation and glaucomatous changes in DBA/2J and DBA/2J-Rj mice. Investigative ophthalmology & visual science 50 18235006
2007 Molecular basis of Diamond-Blackfan anemia: structure and function analysis of RPS19. Nucleic acids research 50 17726054
2015 Immune Response of Calves Vaccinated with Brucella abortus S19 or RB51 and Revaccinated with RB51. PloS one 49 26352261
2008 The Brucella abortus S19 DeltavjbR live vaccine candidate is safer than S19 and confers protection against wild-type challenge in BALB/c mice when delivered in a sustained-release vehicle. Infection and immunity 47 19047401
2014 Defects of protein production in erythroid cells revealed in a zebrafish Diamond-Blackfan anemia model for mutation in RPS19. Cell death & disease 46 25058426
1995 Protein and molecular characterization of hippocampal protein kinase C in C57BL/6 and DBA/2 mice. Journal of neurochemistry 46 7760054
2021 BCLXL gene therapy moderates neuropathology in the DBA/2J mouse model of inherited glaucoma. Cell death & disease 45 34376637
2003 Proliferation deficiency of multipotent hematopoietic progenitors in ribosomal protein S19 (RPS19)-deficient diamond-Blackfan anemia improves following RPS19 gene transfer. Molecular therapy : the journal of the American Society of Gene Therapy 45 12718904
2000 Ribosomal protein S19 gene mutations in patients with diamond-blackfan anemia and identification of ribosomal protein S19 pseudogenes. Blood cells, molecules & diseases 44 10753603
1988 Expression of the rpl23, rpl2 and rps19 genes in spinach chloroplasts. Nucleic acids research 43 3362671
2007 Roles of the ribosomal protein S19 dimer and the C5a receptor in pathophysiological functions of phagocytic leukocytes. Pathology international 41 17199736
2019 QiShenYiQi Pills® ameliorates ischemia/reperfusion-induced myocardial fibrosis involving RP S19-mediated TGFβ1/Smads signaling pathway. Pharmacological research 40 31085230
2009 Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush. BMC neuroscience 40 19643015
2005 Interactions between RPS19, mutated in Diamond-Blackfan anemia, and the PIM-1 oncoprotein. Haematologica 40 16266891
2020 Complement peptide C3a receptor 1 promotes optic nerve degeneration in DBA/2J mice. Journal of neuroinflammation 39 33176797
2012 Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer. PloS one 38 22496757
2010 Interaction of hantavirus nucleocapsid protein with ribosomal protein S19. Journal of virology 38 20844026
2014 p53-Independent cell cycle and erythroid differentiation defects in murine embryonic stem cells haploinsufficient for Diamond Blackfan anemia-proteins: RPS19 versus RPL5. PloS one 37 24558476
2011 Characterization of the Interaction between hantavirus nucleocapsid protein (N) and ribosomal protein S19 (RPS19). The Journal of biological chemistry 37 21296889
2009 Ribosomal protein S19 and S24 insufficiency cause distinct cell cycle defects in Diamond-Blackfan anemia. Biochimica et biophysica acta 37 19689926
2004 Nonsense-mediated and nonstop decay of ribosomal protein S19 mRNA in Diamond-Blackfan anemia. Human mutation 36 15523650
2009 Characterization of pharmacological and behavioral differences to nicotine in C57Bl/6 and DBA/2 mice. Neuropharmacology 35 19619563
1999 Truncating ribosomal protein S19 mutations and variable clinical expression in Diamond-Blackfan anemia. Human genetics 35 10598818
2007 Transcriptional profiling of C57 and DBA strains of mice in the absence and presence of morphine. BMC genomics 34 17367521
2000 Diamond-Blackfan anemia: report of seven further mutations in the RPS19 gene and evidence of mutation heterogeneity in the Italian population. Blood cells, molecules & diseases 34 11112378
2013 Ribosomal protein S19 is a novel therapeutic agent in inflammatory kidney disease. Clinical science (London, England : 1979) 33 23252627
2001 Identification of receptor-binding sites of monocyte chemotactic S19 ribosomal protein dimer. The American journal of pathology 33 11733378
2015 Neurodegeneration and Vision Loss after Mild Blunt Trauma in the C57Bl/6 and DBA/2J Mouse. PloS one 31 26148200
1994 The S12 ribosomal protein of Podospora anserina belongs to the S19 bacterial family and controls the mitochondrial genome integrity through cytoplasmic translation. The Journal of biological chemistry 31 8195128
2005 High specificity of combined TRAP and DBA.44 expression for hairy cell leukemia. The American journal of surgical pathology 30 15767800
2023 An RPS19-edited model for Diamond-Blackfan anemia reveals TP53-dependent impairment of hematopoietic stem cell activity. JCI insight 29 36413407
2014 Gene therapy cures the anemia and lethal bone marrow failure in a mouse model of RPS19-deficient Diamond-Blackfan anemia. Haematologica 29 25216681
2010 C57BL/6J, DBA/2J, and DBA/2J.Gpnmb mice have different visual signal processing in the inner retina. Molecular vision 29 21203347
2015 A Murine Hypertrophic Cardiomyopathy Model: The DBA/2J Strain. PloS one 28 26241864
2014 Ly49 receptors activate angiogenic mouse DBA⁺ uterine natural killer cells. Cellular & molecular immunology 26 24954223
1996 Anticonvulsant effect of reduced NMDA receptor expression in audiogenic DBA/2 mice. Epilepsy research 25 8985683
2017 Mesenchymal Stem Cell Therapy Prevents Abortion in CBA/J × DBA/2 Mating. Reproductive sciences (Thousand Oaks, Calif.) 24 29187052
2003 Ten novel Diamond-Blackfan anemia mutations and three polymorphisms within the rps19 gene. The hematology journal : the official journal of the European Haematology Association 24 12750732
2014 Ribosomal protein S19-binding domain provides insights into hantavirus nucleocapsid protein-mediated translation initiation mechanism. The Biochemical journal 23 25062117
2013 Transcriptome analysis of the zebrafish model of Diamond-Blackfan anemia from RPS19 deficiency via p53-dependent and -independent pathways. PloS one 23 23990987
2012 Pregabalin- and topiramate-mediated regulation of cognitive and motor impulsivity in DBA/2 mice. British journal of pharmacology 23 22489711
2008 Deficient RPS19 protein production induces cell cycle arrest in erythroid progenitor cells. British journal of haematology 23 18217898
2011 Localization and phenotype-specific expression of ryanodine calcium release channels in C57BL6 and DBA/2J mouse strains. Experimental eye research 22 21933672
2016 Depletion of ribosomal protein S19 causes a reduction of rRNA synthesis. Scientific reports 21 27734913
2015 Attenuation of hearing loss in DBA/2J mice by anti-apoptotic treatment. Hearing research 21 26003529
2008 Differences in DBA/1J and DBA/2J reveal lipid QTL genes. Journal of lipid research 21 18503028
2005 A novel nucleolar protein interacts with ribosomal protein S19. Biochemical and biophysical research communications 20 16289379
1986 Acute and chronic acetazolamide administration in DBA and C57 mice: effects of age. Epilepsia 20 3081335
2008 Study of the effects of proteasome inhibitors on ribosomal protein S19 (RPS19) mutants, identified in patients with Diamond-Blackfan anemia. Haematologica 18 18768533
2022 QiShenYiQi Pill Ameliorates Cardiac Fibrosis After Pressure Overload-Induced Cardiac Hypertrophy by Regulating FHL2 and the Macrophage RP S19/TGF-β1 Signaling Pathway. Frontiers in pharmacology 17 35910357
2017 DBA/2J Haplotype on Distal Chromosome 2 Reduces Mertk Expression, Restricts Efferocytosis, and Increases Susceptibility to Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 17 28473436
2013 Altered expression of nNOS/NIDD in the retina of a glaucoma model of DBA/2J mice and the intervention by nNOS inhibition. Journal of molecular neuroscience : MN 17 23297011
2019 Czech and Slovak Diamond-Blackfan Anemia (DBA) Registry update: Clinical data and novel causative genetic lesions. Blood cells, molecules & diseases 15 31855845
2014 Clinical phenotype and genetic analysis of RPS19, RPL5, and RPL11 genes in Greek patients with Diamond Blackfan Anemia. Pediatric blood & cancer 15 25132370
2010 Base of molecular mimicry between human ribosomal protein S19 dimer and human C5a anaphylatoxin. International immunopharmacology 15 20869475
2009 Phosphorylation of ribosomal protein S19 at Ser59 by CaM kinase I alpha. Journal of neurochemistry 15 19200342
2006 The functions of RPS19 and their relationship to Diamond-Blackfan anemia: a review. Molecular genetics and metabolism 15 17178250
1993 Mainstream and sidestream cigarette smoke-induced DNA adducts in C7Bl and DBA mice. Environmental health perspectives 15 8319637
2021 Amphioxus ribosomal proteins RPS15, RPS18, RPS19 and RPS30-precursor act as immune effectors via killing or agglutinating bacteria. Fish & shellfish immunology 14 34487827
2021 Brucella abortus S19 GFP-tagged vaccine allows the serological identification of vaccinated cattle. PloS one 13 34807952
2015 The evolutionary conservation of rps3 introns and rps19-rps3-rpl16 gene cluster in Adiantum capillus-veneris mitochondria. Current genetics 13 26281979
2010 Comparison of C57BL/6 and DBA/2 mice in food motivation and satiety. Physiology & behavior 13 20138902
2004 Guinea pig S19 ribosomal protein as precursor of C5a receptor-directed monocyte-selective leukocyte chemotactic factor. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 13 15693611

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