Affinage

RPL22

Large ribosomal subunit protein eL22 · UniProt P35268

Length
128 aa
Mass
14.8 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL22 (eL22) is a component of the 60S ribosomal large subunit that doubles as a sequence-specific RNA-binding protein with extensive extraribosomal regulatory functions in development, stress responses, and tumor suppression (PMID:8159770, PMID:17555992). Within the ribosome its protruding beta-hairpin lines the polypeptide exit tunnel and contacts 23S/28S rRNA; mutations in this hairpin remodel the tunnel and confer macrolide resistance (PMID:9862810, PMID:11511371, PMID:12225755), and high-affinity rRNA binding through basic residues 80-93 drives both nucleolar accumulation and ribosome incorporation (PMID:19390581). Independently of the ribosome, RPL22 recognizes a stem-loop RNA motif defined by SELEX (PMID:7494316), first identified through its binding to three stem-loops of the EBV non-coding RNA EBER1, which relocalizes RPL22 from the nucleolus to the nucleoplasm and promotes lymphoma cell growth (PMID:8380232, PMID:16556938, PMID:19640998). A dominant physiological role is restraint of p53: RPL22 post-transcriptionally represses p53 mRNA translation—an activity transcriptionally driven by Miz-1—to protect lymphoid progenitors undergoing V(D)J recombination, and germline Rpl22 loss triggers p53-dependent, PUMA/Bim-mediated arrest of alphabeta T cell and pro-B cell development at lineage-specific checkpoints, in part via PERK-coupled ER stress (PMID:17555992, PMID:25468973, PMID:21690328, PMID:25416806, PMID:27489283). RPL22 also acts as a nuclear splicing regulator, binding intronic and exonic sequences of smad2 and MDM4 pre-mRNAs to control Nodal/TGF-beta signaling and MDM4 isoform output in functional antagonism with its paralog RPL22L1, whose expression RPL22 directly represses to govern ribosome heterogeneity (PMID:28076796, PMID:39146182, PMID:23990801). Loss-of-function in lymphoid cells is oncogenic, inducing the stemness factor Lin28B and accelerating thymic lymphoma (PMID:22976955).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1991 High

    Established the protein's existence as a discrete cellular RNA-binding factor (EAP) physically associated with EBV small RNAs, before its ribosomal identity was known.

    Evidence Protein purification, cDNA cloning, and RNA co-immunoprecipitation of EBER1/EBER2-associated protein

    PMID:1846807

    Open questions at the time
    • Did not identify EAP as ribosomal protein L22
    • Functional consequence of EBER binding unknown
  2. 1993 High

    Demonstrated that RNA recognition is direct and sequence-specific, mapping binding to a defined EBER1 stem-loop without requiring other factors.

    Evidence Gel-shift and RNase protection with recombinant GST-EAP, EBER1 mutational analysis

    PMID:8380232

    Open questions at the time
    • Cellular RNA ligands beyond EBER1 not yet defined
    • No consensus binding motif
  3. 1994 High

    Resolved that EAP is ribosomal protein L22 and showed EBER1 binding redistributes a pool of L22 to the nucleoplasm, defining its dual ribosomal/extraribosomal nature.

    Evidence Immunofluorescence, subcellular fractionation, in situ hybridization, in vitro binding; plus independent heparin-affinity identification as HBp15

    PMID:8135813 PMID:8159770

    Open questions at the time
    • Mechanism partitioning L22 between ribosome and EBER1 RNP unclear
    • Whether relocalized L22 has a function not addressed
  4. 1995 High

    Defined a general stem-loop RNA recognition motif for L22 and identified a cellular 28S rRNA ligand, generalizing its RNA-binding specificity beyond EBER1.

    Evidence SELEX, cDNA-SELEX, and mobility shift assays

    PMID:7494316

    Open questions at the time
    • mRNA targets not yet identified
    • Functional readout of motif binding absent
  5. 1998 High

    Determined the L22 fold and localized the antibiotic-resistance-conferring beta-hairpin, linking protein structure to the ribosome exit tunnel.

    Evidence X-ray crystallography of T. thermophilus L22

    PMID:9862810

    Open questions at the time
    • Dynamics of hairpin in intact ribosome not shown
    • Mammalian structural details inferred from bacterial protein
  6. 2002 High

    Connected L22 hairpin geometry to tunnel architecture by showing a resistance-conferring deletion bends the hairpin into the tunnel, and cryo-EM linked L22/L4 to a dynamic multi-exit tunnel system.

    Evidence X-ray crystallography of L22 mutant, chemical rRNA probing, cryo-EM of resistant 70S ribosomes

    PMID:10369764 PMID:11511371 PMID:12225755

    Open questions at the time
    • Functional consequence of tunnel gating for nascent chains not defined
    • Bacterial system; mammalian relevance assumed
  7. 2009 High

    Showed that RNA binding (not a discrete signal) drives nucleolar localization and ribosome incorporation, unifying L22's RNA-recognition activity with its assembly behavior.

    Evidence Mutagenesis of residues 80-93 with RNA binding, GFP localization, and ribosome incorporation readouts; earlier import signal mapping

    PMID:11056215 PMID:19390581

    Open questions at the time
    • How the same residues toggle between rRNA and mRNA targets unclear
    • Regulation of ribosome-free pool not addressed here
  8. 2007 High

    Revealed a physiological extraribosomal role: Rpl22 loss selectively arrests alphabeta T cell development via p53 induction, defining lineage-specific p53 control as a core function.

    Evidence Germline knockout mice with p53 epistasis and thymocyte death assays

    PMID:17555992

    Open questions at the time
    • Molecular basis of p53 upregulation not yet defined
    • Why gammadelta lineage is spared unexplained
  9. 2014 High

    Established the molecular mechanism of p53 control—Miz-1 transcriptionally activates Rpl22, whose protein binds p53 mRNA to repress its translation in recombining lymphoid progenitors.

    Evidence ChIP, RNA-protein binding assays, p53 level analysis in Miz-1-deficient cells; earlier PUMA/Bim epistasis and B cell extension

    PMID:21690328 PMID:25416806 PMID:25468973

    Open questions at the time
    • Direct binding site on p53 mRNA not finely mapped
    • Quantitative contribution of translational vs other control not resolved
  10. 2016 High

    Placed an ER-stress/PERK axis upstream of p53 in the developmental arrest, refining how Rpl22 loss converges on p53 in a lineage-selective manner.

    Evidence Knockout mice, pharmacological ER stress, PERK knockdown, p53 readouts

    PMID:27489283

    Open questions at the time
    • How Rpl22 loss elevates ER stress mechanistically unclear
    • Link between ribosomal change and PERK activation undefined
  11. 2013 High

    Defined how Rpl22 governs ribosome heterogeneity by directly repressing its paralog Rpl22l1 via hairpin binding, with compensatory Rpl22l1 incorporation upon loss.

    Evidence Knockout mice, RNA-binding assays, ribosome fractionation, knockdown rescue; later refined as cryptic-exon splicing repression

    PMID:23990801 PMID:39146182

    Open questions at the time
    • Functional consequences of paralog-swapped ribosomes incompletely defined
    • Whether repression is purely translational vs splicing-based clarified only later
  12. 2017 High

    Identified RPL22 as a nuclear pre-mRNA splicing regulator acting antagonistically with RPL22L1 on smad2 to control Nodal/TGF-beta signaling, broadening its extraribosomal repertoire beyond p53.

    Evidence Nuclear fractionation, RIP on smad2 introns, splicing assays, hnRNP-A1 interaction, zebrafish morphogenesis; MDM2-binding p53 stabilization and CDK4-Cyclin D1 inhibition reported same era

    PMID:28076796 PMID:29207594 PMID:30874462

    Open questions at the time
    • Determinants directing RPL22 to specific introns unknown
    • Stoichiometry and trigger of nuclear translocation undefined
  13. 2024 Medium

    Extended splicing control to MDM4 exon 6, linking RPL22 loss to MDM4 isoform switching, increased proliferation, and Nutlin-3a resistance, integrating its splicing and p53-axis roles.

    Evidence Splicing assays, loss-of-function frameshift mutants, isoform quantification, proliferation and drug-resistance assays

    PMID:39146182

    Open questions at the time
    • Direct binding site on MDM4 pre-mRNA not mapped
    • Single-lab; in vivo relevance to tumors not tested
  14. 2020 Medium

    Showed RPL22 post-transcriptionally represses CCL2 by binding its 5'UTR and recruiting UPF1 for cytoplasmic mRNA degradation, extending mRNA-target regulation to inflammation.

    Evidence RNA-binding assay, RPL22-UPF1 Co-IP, nuclear translocation and knockdown with monocyte migration readout

    PMID:32383535

    Open questions at the time
    • Reciprocal validation of UPF1 interaction limited
    • Single lab; generality across inflammatory stimuli untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RPL22 selects among its many RNA targets (rRNA, viral non-coding RNAs, paralog mRNA, p53 mRNA, CCL2 mRNA, smad2/MDM4 pre-mRNAs) and how the ribosome-free pool is dynamically generated and directed between cytoplasmic translational repression and nuclear splicing remains unresolved.
  • No unifying model coupling ribosome occupancy to target choice
  • Post-translational regulation of pool partitioning unknown
  • Structural basis for distinguishing mRNA targets from rRNA undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 9 GO:0005198 structural molecule activity 4 GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 3
Localization
GO:0005654 nucleoplasm 4 GO:0005840 ribosome 4 GO:0005634 nucleus 3 GO:0005730 nucleolus 3 GO:0005829 cytosol 3
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1640170 Cell Cycle 2 R-HSA-8953897 Cellular responses to stimuli 1
Partners
CDK4HNRNP-A1MDM2RPL11RPL22L1RPL5UPF1
Complex memberships
60S ribosomal large subunitEBER1 ribonucleoprotein particleMDM2/RPL5/RPL11/RPL22 complex

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 EAP (later identified as RPL22/L22) is a 14,777 Da, 128 amino acid cellular RNA-binding protein that associates with Epstein-Barr virus small RNAs EBER1 and EBER2. Purification and cDNA cloning revealed a potential nuclear localization signal and highly acidic carboxy terminus. Protein purification, cDNA cloning, RNA co-immunoprecipitation The EMBO journal High 1846807
1993 RPL22/EAP binds a specific stem-loop structure (stem-loop 3) of EBER1 in a sequence-specific manner, recognizing both single-stranded and double-stranded regions. Bacterially expressed GST-EAP fusion protein binds EBER1 independently of any other cellular or viral protein. A second, weaker binding site exists on stem-loop 4. RNase protection assay, gel-shift assay with recombinant GST-EAP fusion protein, EBER1 deletion and mutational analysis, anti-EAP immunoprecipitation Molecular and cellular biology High 8380232
1994 EAP is the ribosomal protein L22. Approximately half of L22 in EBV-positive cells is contained within the EBER1 RNP particle; the other half resides in monoribosomes and polysomes. In EBV-positive lymphocytes, L22 is relocalized from the cytoplasm/nucleolus to the nucleoplasm through binding to EBER1. In vitro incubation of uninfected cell extracts with excess EBER1 RNA does not remove L22 from pre-existing ribosomes, suggesting in vivo EBER1 binding precedes ribosome assembly. Immunofluorescence with anti-L22 antibodies, subcellular fractionation (monoribosomes/polysomes), in situ hybridization, in vitro binding assay Proceedings of the National Academy of Sciences of the United States of America High 8159770
1994 RPL22/L22 is a heparin-binding protein (HBp15) purified from submandibular gland and bovine brain, identified as mammalian ribosomal protein L22 by antibody recognition of a single polypeptide in the large ribosomal subunit fraction. Heparin-affinity purification, immunochemical analysis of subcellular fractions, cDNA cloning and sequencing Biochemical and biophysical research communications Medium 8135813
1995 SELEX analysis identified a stem-loop motif as the general L22-binding RNA element, with three conserved nucleotide positions. Two independent L22 binding sites exist on EBER1 and two L22 molecules can interact with EBER1 simultaneously. Human 28S rRNA stem-loop (nucleotides 302-317) was identified as a cellular L22 ligand via cDNA-SELEX. SELEX (systematic evolution of ligands by exponential enrichment), mobility shift assays, cDNA-derived RNA library selection Journal of virology High 7494316
1996 RPL22/EAP interacts with the DNA-binding domain of HSV-1 ICP4. GST-EAP fusion protein disrupts ICP4 binding to its cognate DNA site in a dose-dependent manner. Late in infection, EAP is translocated from nucleoli to colocalize with ICP4 in small dense nuclear structures, a process dependent on viral DNA synthesis. Gel-shift assay, GST fusion protein pulldown, immunofluorescence colocalization, viral mutant analysis Proceedings of the National Academy of Sciences of the United States of America Medium 8643445
1998 Crystal structure of Thermus thermophilus L22 was solved by X-ray crystallography. L22 consists of a small alpha+beta domain and a protruding beta hairpin (30 Å long). The erythromycin-resistance conferring mutation is located in the protruding beta hairpin, predicted to interact with the erythromycin-binding site near the peptidyl transferase center. X-ray crystallography Structure (London, England : 1993) High 9862810
1999 Erythromycin resistance mutations in L22 (and L4) perturb rRNA conformation at multiple sites in domains II, III, and V of 23S rRNA, despite these proteins binding primarily to domain I. The L22 mutation influences modification at positions m5U747, G748, A1268 (domain II), A1614 (domain III), and G2351 (domain V). Neither L22 nor L4 mutations produce detectable effects at A2058 in domain V. Chemical modification/probing of 23S rRNA in erythromycin-resistant E. coli ribosomes bearing L22 and L4 mutations Journal of molecular biology High 10369764
2000 Nuclear import of human RPL22 depends on a classical nuclear localization signal (four lysines at positions 13-16). Nucleolar entry requires the KKYLKK sequence (I-domain, positions 88-93). The C-terminal acidic residue cluster plays a nuclear retention role, concealed by weak interaction with the N-domain (positions 1-9). Assembly into the ribosome depends on the N-domain, which upon dissociation from its interaction with the C-domain, binds to 28S rRNA. Deletion mutagenesis, yeast two-hybrid (N-domain/C-domain interaction), subcellular localization studies FEBS letters Medium 11056215
2001 Cryo-electron microscopy of erythromycin-resistant E. coli 70S ribosomes with L4 and L22 mutations reveals that ribosomal proteins L4 and L22 may be involved in the regulation of a multiple exit system in the large subunit tunnel, with opening and closing of the main tunnel being dynamic features possibly accompanied by changes in the L7/L12 stalk region. Cryo-electron microscopy (3D reconstruction) of erythromycin-resistant ribosomes Molecular cell High 11511371
2002 A three-amino-acid deletion (equivalent of MKR triplet) in the protruding beta hairpin of L22 that interacts with 23S rRNA renders cells resistant to erythromycin and quinupristin. Crystal structure of the Thermus thermophilus L22 mutant at 1.8 Å shows the mutant beta-hairpin is bent inward into the ribosome tunnel, modifying the narrowest part of the tunnel and affecting the orientation of 23S rRNA nucleotides that form the erythromycin-binding pocket. X-ray crystallography of L22 mutant, structural superposition within 50S subunits from H. marismortui and D. radiodurans Journal of molecular biology High 12225755
2004 L22 and PKR compete for a common binding site on EBER-1. L22 interferes with the ability of EBER-1 to inhibit PKR activation by dsRNA. Expression of L22 prevents both PKR-dependent and -independent stimulatory effects of EBER-1 on gene expression in vivo. RNA-protein competition binding assays, reporter gene assays in murine embryonic fibroblasts, PKR knockout cells European journal of biochemistry Medium 15128299
2006 EBER1 contains three L22 binding sites (stem-loops I, III, and IV), and up to three L22 molecules can bind per EBER1 molecule simultaneously. In vivo UV cross-linking confirms multiple L22 binding sites on EBER1 inside cells. EMSA with purified recombinant L22 and MBP-L22, EBER1 deletion constructs, EBER1 stem-loop insertion into non-binding RNA, in vivo UV cross-linking RNA (New York, N.Y.) High 16556938
2007 Germline ablation of Rpl22 in mice selectively arrests development of alphabeta T lineage cells at the beta-selection checkpoint by inducing cell death. The death is caused by induction of p53 expression, as p53 deficiency blocks death and restores development. Rpl22 deficiency leads to selective upregulation of p53 at least in part by increasing p53 synthesis. gammadelta T lineage cells are spared. Conditional/germline knockout mice, flow cytometry, genetic epistasis (p53-deficient background), thymocyte death assays Immunity High 17555992
2009 Basic amino acids 80-93 of L22 are required for high-affinity binding to 28S rRNA and EBER-1. These same residues are also critical for nucleolar accumulation and incorporation into ribosomes, supporting the model that nucleolar localization is mediated by rRNA interaction rather than a defined localization signal. Mutagenesis of L22, RNA-protein binding assays, GFP-tagged mutant localization by fluorescence microscopy, ribosome incorporation assay PloS one High 19390581
2009 EBER-1-mediated relocalization of L22 from nucleolus to nucleoplasm requires intact L22 binding sites on EBER-1. Mutation of L22 binding sites on EBER-1 prevents L22 binding, inhibits EBER-1-dependent L22 relocalization, and significantly reduces the capacity of EBER-1 to enhance cell growth potential in soft agar colony formation assays. RNA-protein binding assays, fluorescence localization studies, soft agar colony formation assay in Burkitt lymphoma cells expressing mutant EBER-1 Journal of virology High 19640998
2012 Monoallelic germline inactivation of Rpl22 predisposes T-lineage progenitors to transformation by inducing expression of the stemness factor Lin28B. Rpl22 inactivation accelerates thymic lymphoma development and increases transformation potential through Lin28B induction. Mouse genetic model (Rpl22 heterozygous knockout), thymic lymphoma assay, in vitro transformation assays, Lin28B expression analysis Blood Medium 22976955
2013 Rpl22 controls ribosome composition by directly repressing expression of its paralog Rpl22l1 through binding to an internal hairpin structure in Rpl22l1 mRNA. Loss of Rpl22 results in compensatory upregulation and incorporation of Rpl22l1 into ribosomes. Rpl22 knockout mice, RNA-binding assays (Rpl22 binding to Rpl22l1 mRNA hairpin), ribosome fractionation, Rpl22l1 knockdown rescue experiments PLoS genetics High 23990801
2014 Miz-1 directly activates the Rpl22 gene, and RPL22 protein binds to p53 mRNA and negatively regulates its translation. This mechanism limits p53 expression levels in pro-B and DN3a pre-T cells undergoing V(D)J recombination, protecting them from DNA damage-induced apoptosis. ChIP (Miz-1 binding to Rpl22 promoter), RNA-protein binding assays (RPL22 binding to p53 mRNA), p53 protein level analysis in Miz-1 deficient cells, genetic epistasis Proceedings of the National Academy of Sciences of the United States of America High 25468973
2016 Loss of Rpl22 exacerbates ER stress selectively in alphabeta T cell progenitors but not gammadelta progenitors. The exacerbated ER stress leads to PERK-dependent p53 induction and selective arrest of alphabeta T cells. Pharmacological induction of ER stress replicates the selective block, and PERK knockdown blunts p53 induction and rescues development. Rpl22 knockout mice, pharmacological ER stress induction, PERK knockdown, p53 measurement, T cell development assays by flow cytometry Journal of immunology (Baltimore, Md. : 1950) High 27489283
2016 Biallelic loss of Rpl22 restricts lymphoma dissemination by downregulating KLF2 transcription factor and its target sphingosine 1-phosphate receptor 1 (S1PR1). Re-expression of S1PR1 in Rpl22-deficient tumor cells restores their migratory capacity in vitro. Rpl22 knockout crossed to lymphoma-prone AKT2-Tg or PTEN-deficient mice, S1PR1 re-expression rescue assay, KLF2/S1PR1 expression analysis Cancer research Medium 27197189
2017 RPL22/eL22 binds to MDM2 acidic domain and inhibits MDM2-mediated p53 ubiquitination and degradation, extending p53 half-life. RPL22 forms a complex with MDM2/RPL5(uL18)/RPL11(uL5) and synergizes with RPL11 to activate p53. The N-terminus of RPL22 binds MDM2, while the C-terminus interacts with RPL5/RPL11. Ribosomal stress by Actinomycin D increases the ribosome-free RPL22 pool. Co-immunoprecipitation, GST pulldown (domain mapping), ubiquitination assay, colony formation assay (p53-dependent), ribosome profiling Oncotarget Medium 29207594
2017 Rpl22 and its paralog Rpl22l1 (Like1) play antagonistic extraribosomal roles in controlling morphogenesis. During gastrulation, Rpl22 translocates to the nucleus where it binds intronic sequences of smad2 pre-mRNA and induces exon 9 skipping in cooperation with hnRNP-A1. Like1 opposes this by promoting exon 9 inclusion. This antagonistic splicing regulation controls Nodal/TGF-β signaling during zebrafish embryogenesis. Nuclear localization studies (fractionation), RNA-immunoprecipitation (Rpl22 binding to smad2 pre-mRNA intron), splicing assays, hnRNP-A1 interaction, zebrafish morpholino/overexpression morphogenesis assays Cell reports High 28076796
2019 RPL22/eL22 binds and inhibits CDK4-Cyclin D1 complex, decreasing RB phosphorylation both in vitro and in cells. Ribosome-free RPL22/eL22 enforces a cell cycle arrest that induces an RB- and p53-dependent senescent phenotype in human fibroblasts. In vitro kinase assay (CDK4-CyclinD1 inhibition), co-immunoprecipitation, RB phosphorylation measurement, senescence assays with RPL22 overexpression Cell cycle (Georgetown, Tex.) Medium 30874462
2020 RPL22 binds to the first 20 nucleotides of the 5'UTR of CCL2 mRNA following LPS stimulation, and translocates to the nucleus. RPL22 interaction with UPF1 (up-frameshift-1 protein) results in cytoplasmic degradation of CCL2 mRNA, post-transcriptionally regulating CCL2 expression and monocyte migration during LPS-mediated inflammation. RNA-protein binding assay (RPL22 binding to CCL2 5'UTR), co-immunoprecipitation (RPL22-UPF1 interaction), nuclear translocation assay, RPL22 knockdown with CCL2 expression and monocyte migration readout The FEBS journal Medium 32383535
2024 RPL22 modulates splicing of MDM4 pre-mRNA through an alternative splicing switch in exon 6. RPL22 loss increases MDM4 exon 6 inclusion and cell proliferation, augmenting resistance to Nutlin-3a. RPL22 also represses RPL22L1 expression by mediating splicing of a cryptic exon corresponding to a truncated transcript. Splicing assays, RPL22 loss-of-function (frameshift mutations), MDM4 splicing isoform quantification, proliferation assays, Nutlin-3a resistance assays Cell reports Medium 39146182
1999 Drosophila RPL22 (PBP-12) interacts with the auto-modification domain of Drosophila PARP through the conserved core of rpL22. Purified DmCKII can phosphorylate a GST-L22 fusion protein at the C-terminal end, identifying RPL22 as a substrate of CKII. Far-Western screening, GST-rpL22 fusion protein pulldown, in vitro kinase assay Gene Low 9931508
2002 Drosophila CKII catalytic subunit interacts with Drosophila ribosomal protein L22 via the conserved core of rpL22, as shown by yeast two-hybrid and GST pulldown. CKII phosphorylates L22 at its C-terminal end in vitro. Yeast two-hybrid, GST pulldown, in vitro kinase assay Biochemical and biophysical research communications Low 12379220
2011 p53-mediated developmental arrest of Rpl22-deficient alphabeta T cells is enforced principally through effects on cell survival via PUMA and Bim. Co-elimination of PUMA and Bim results in nearly complete restoration of Rpl22-deficient thymocyte development. Overexpression of miR-34a causes developmental arrest reminiscent of p53 activation in Rpl22-deficient T cells. Genetic epistasis (double KO of PUMA/Bim, p21, miR-34a overexpression), flow cytometry of thymocyte development, gene expression analysis Journal of immunology (Baltimore, Md. : 1950) High 21690328
2015 Germline ablation of Rpl22 causes a selective p53-dependent arrest of early B cell development at the pro-B cell stage in bone marrow. Rpl22-deficient pro-B cells are hyporesponsive to IL-7, but the arrest does not result from disrupted IL-7 signaling. p53 deficiency rescues the B cell developmental defect. Germline Rpl22 KO mice, flow cytometry, IL-7 signaling analysis, p53 KO epistasis Journal of immunology (Baltimore, Md. : 1950) High 25416806
2016 In S. cerevisiae, Rpl22A and Rpl22B are required for selective translation of IME1 mRNA through its unusually long 5'UTR, required for meiotic induction. Rpl22 maintains high free 60S subunit levels under conditions of high translational output, preventing halfmer formation. Deleting the IME1 5'UTR bypasses the requirement for Rpl22. Rpl22 yeast mutants, polysome profiling, 5'UTR deletion analysis, Ime1 protein level measurement, meiotic phenotype assays Cell division Medium 27478489

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 The 3;21 translocation in myelodysplasia results in a fusion transcript between the AML1 gene and the gene for EAP, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1. Proceedings of the National Academy of Sciences of the United States of America 197 8395054
2007 Ablation of ribosomal protein L22 selectively impairs alphabeta T cell development by activation of a p53-dependent checkpoint. Immunity 157 17555992
2001 The polypeptide tunnel system in the ribosome and its gating in erythromycin resistance mutants of L4 and L22. Molecular cell 156 11511371
1994 The Epstein-Barr virus (EBV) small RNA EBER1 binds and relocalizes ribosomal protein L22 in EBV-infected human B lymphocytes. Proceedings of the National Academy of Sciences of the United States of America 137 8159770
2010 Complete plastid genome sequences of three Rosids (Castanea, Prunus, Theobroma): evidence for at least two independent transfers of rpl22 to the nucleus. Molecular biology and evolution 134 20935065
2012 Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B. Blood 125 22976955
1999 Erythromycin resistance mutations in ribosomal proteins L22 and L4 perturb the higher order structure of 23 S ribosomal RNA. Journal of molecular biology 112 10369764
2013 The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1. PLoS genetics 107 23990801
1991 EAP, a highly conserved cellular protein associated with Epstein-Barr virus small RNAs (EBERs). The EMBO journal 95 1846807
1997 Association of herpes simplex virus regulatory protein ICP22 with transcriptional complexes containing EAP, ICP4, RNA polymerase II, and viral DNA requires posttranslational modification by the U(L)13 proteinkinase. Journal of virology 86 8995634
2003 The adhesive and immunomodulating properties of the multifunctional Staphylococcus aureus protein Eap. Microbiology (Reading, England) 84 14523103
2017 Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing. Cell reports 81 28076796
2005 The extracellular adherence protein (Eap) of Staphylococcus aureus inhibits wound healing by interfering with host defense and repair mechanisms. Blood 81 16317095
2007 Novel mutations in ribosomal proteins L4 and L22 that confer erythromycin resistance in Escherichia coli. Molecular microbiology 77 17956547
1995 In vitro selection of RNA ligands for the ribosomal L22 protein associated with Epstein-Barr virus-expressed RNA by using randomized and cDNA-derived RNA libraries. Journal of virology 74 7494316
1976 Isolation of eukaryotic ribosomal proteins. Purification and characterization of the 60 S ribosomal subunit proteins L4, L5, L7, L9, L11, L12, L13, L21, L22, L23, L26, L27, L30, L33, L35', L37, and L39. The Journal of biological chemistry 70 1002715
2005 sae is essential for expression of the staphylococcal adhesins Eap and Emp. Microbiology (Reading, England) 68 15941988
2020 Durvalumab after definitive chemoradiotherapy in locally advanced unresectable non-small cell lung cancer (NSCLC): Real-world data on survival and safety from the German expanded-access program (EAP). Lung cancer (Amsterdam, Netherlands) 66 33126091
2006 Multiple domains of EBER 1, an Epstein-Barr virus noncoding RNA, recruit human ribosomal protein L22. RNA (New York, N.Y.) 66 16556938
1998 Non-obese diabetic (NOD) mice are genetically susceptible to experimental autoimmune prostatitis (EAP). Journal of autoimmunity 64 9878082
2002 Insertional inactivation of Eap in Staphylococcus aureus strain Newman confers reduced staphylococcal binding to fibroblasts. Infection and immunity 62 12010982
2012 Frequent mutations in the RPL22 gene and its clinical and functional implications. Gynecologic oncology 61 23127973
2010 Surfactant protein A (SP-A)-mediated clearance of Staphylococcus aureus involves binding of SP-A to the staphylococcal adhesin eap and the macrophage receptors SP-A receptor 210 and scavenger receptor class A. The Journal of biological chemistry 61 21123169
2002 Resistance to quinupristin-dalfopristin due to mutation of L22 ribosomal protein in Staphylococcus aureus. Antimicrobial agents and chemotherapy 61 12069975
2010 Proteomic analysis of rodent ribosomes revealed heterogeneity including ribosomal proteins L10-like, L22-like 1, and L39-like. Journal of proteome research 60 20063902
2005 The crystal structures of EAP domains from Staphylococcus aureus reveal an unexpected homology to bacterial superantigens. The Journal of biological chemistry 59 15691839
2009 Growth-promoting properties of Epstein-Barr virus EBER-1 RNA correlate with ribosomal protein L22 binding. Journal of virology 56 19640998
2017 Vitamin D in European children-statement from the European Academy of Paediatrics (EAP). European journal of pediatrics 55 28401345
1996 The chimeric genes AML1/MDS1 and AML1/EAP inhibit AML1B activation at the CSF1R promoter, but only AML1/MDS1 has tumor-promoter properties. Proceedings of the National Academy of Sciences of the United States of America 54 8577711
2007 eap Gene as novel target for specific identification of Staphylococcus aureus. Journal of clinical microbiology 51 18094124
2018 The Staphylococcus aureus Extracellular Adherence Protein Eap Is a DNA Binding Protein Capable of Blocking Neutrophil Extracellular Trap Formation. Frontiers in cellular and infection microbiology 50 30038902
2002 Prostatein or steroid binding protein (PSBP) induces experimental autoimmune prostatitis (EAP) in NOD mice. Clinical immunology (Orlando, Fla.) 49 12482391
1998 The crystal structure of ribosomal protein L22 from Thermus thermophilus: insights into the mechanism of erythromycin resistance. Structure (London, England : 1993) 49 9862810
2015 IL17 Mediates Pelvic Pain in Experimental Autoimmune Prostatitis (EAP). PloS one 48 25933188
2014 High frequency of RPL22 mutations in microsatellite-unstable colorectal and endometrial tumors. Human mutation 48 25196364
1997 Molecular characteristics of the novel intermediate filament protein paranemin. Sequence reveals EAP-300 and IFAPa-400 are highly homologous to paranemin. The Journal of biological chemistry 48 9405460
2017 Cancer-mutated ribosome protein L22 (RPL22/eL22) suppresses cancer cell survival by blocking p53-MDM2 circuit. Oncotarget 47 29207594
2001 Analogs of Eap protein are conserved and prevalent in clinical Staphylococcus aureus isolates. Clinical and diagnostic laboratory immunology 45 11687475
2004 Ribosomal protein L22 inhibits regulation of cellular activities by the Epstein-Barr virus small RNA EBER-1. European journal of biochemistry 43 15128299
1988 Synthetic peptides derived from IRBP induce EAU and EAP in Lewis rats. Current eye research 41 3262040
1993 The cellular RNA-binding protein EAP recognizes a conserved stem-loop in the Epstein-Barr virus small RNA EBER 1. Molecular and cellular biology 40 8380232
2001 Rebinding of extracellular adherence protein Eap to Staphylococcus aureus can occur through a surface-bound neutral phosphatase. Journal of bacteriology 38 11395464
1992 Expression of the barrier-associated proteins EAP-300 and claustrin in the developing central nervous system. Brain research. Developmental brain research 38 1473281
2016 Rpl22 Loss Selectively Impairs αβ T Cell Development by Dysregulating Endoplasmic Reticulum Stress Signaling. Journal of immunology (Baltimore, Md. : 1950) 37 27489283
2008 Revisiting the mechanism of macrolide-antibiotic resistance mediated by ribosomal protein L22. Proceedings of the National Academy of Sciences of the United States of America 36 19015512
2002 L22 ribosomal protein and effect of its mutation on ribosome resistance to erythromycin. Journal of molecular biology 36 12225755
2015 Ribosomal L22-like1 (RPL22L1) Promotes Ovarian Cancer Metastasis by Inducing Epithelial-to-Mesenchymal Transition. PloS one 34 26618703
1996 Functional interaction and colocalization of the herpes simplex virus 1 major regulatory protein ICP4 with EAP, a nucleolar-ribosomal protein. Proceedings of the National Academy of Sciences of the United States of America 34 8643445
1999 Poly(ADP-ribose) polymerase interacts with novel Drosophila ribosomal proteins, L22 and l23a, with unique histone-like amino-terminal extensions. Gene 33 9931508
2009 Erythromycin resistance by L4/L22 mutations and resistance masking by drug efflux pump deficiency. The EMBO journal 32 19197244
2016 Ribosomal Protein Rpl22 Controls the Dissemination of T-cell Lymphoma. Cancer research 31 27197189
2014 Miz-1 regulates translation of Trp53 via ribosomal protein L22 in cells undergoing V(D)J recombination. Proceedings of the National Academy of Sciences of the United States of America 31 25468973
2011 Developmental arrest of T cells in Rpl22-deficient mice is dependent upon multiple p53 effectors. Journal of immunology (Baltimore, Md. : 1950) 31 21690328
2010 Expression of ribosomal protein L22e family members in Drosophila melanogaster: rpL22-like is differentially expressed and alternatively spliced. Nucleic acids research 31 21138957
2007 The Staphylococcus aureus extracellular adherence protein (Eap) adopts an elongated but structured conformation in solution. Protein science : a publication of the Protein Society 31 18029416
2013 Down-regulation of ribosomal protein L22 in non-small cell lung cancer. Medical oncology (Northwood, London, England) 30 23797773
2000 An acidic amino acid cluster regulates the nucleolar localization and ribosome assembly of human ribosomal protein L22. FEBS letters 30 11056215
2019 Italian Cohort of the Nivolumab EAP in Squamous NSCLC: Efficacy and Safety in Patients With CNS Metastases. Anticancer research 28 31366516
2016 What lies beneath? Diffusion EAP-based study of brain tissue microstructure. Medical image analysis 28 27086167
2019 Redundant and Distinct Roles of Secreted Protein Eap and Cell Wall-Anchored Protein SasG in Biofilm Formation and Pathogenicity of Staphylococcus aureus. Infection and immunity 27 30670553
2015 Rpl22 Loss Impairs the Development of B Lymphocytes by Activating a p53-Dependent Checkpoint. Journal of immunology (Baltimore, Md. : 1950) 27 25416806
2021 Melatonin attenuates prostatic inflammation and pelvic pain via Sirt1-dependent inhibition of the NLRP3 inflammasome in an EAP mouse model. The Prostate 26 34418127
2019 The Hypermethylation of Foxp3 Promoter Impairs the Function of Treg Cells in EAP. Inflammation 25 31209730
2009 Clusters of basic amino acids contribute to RNA binding and nucleolar localization of ribosomal protein L22. PloS one 25 19390581
2023 Ribosomal protein L22-like1 promotes prostate cancer progression by activating PI3K/Akt/mTOR signalling pathway. Journal of cellular and molecular medicine 24 36625246
2019 Ribosomal protein RPL22/eL22 regulates the cell cycle by acting as an inhibitor of the CDK4-cyclin D complex. Cell cycle (Georgetown, Tex.) 24 30874462
2006 The anchorless adhesin Eap (extracellular adherence protein) from Staphylococcus aureus selectively recognizes extracellular matrix aggregates but binds promiscuously to monomeric matrix macromolecules. Matrix biology : journal of the International Society for Matrix Biology 24 16522365
2018 Efficacy and safety data in elderly patients with metastatic renal cell carcinoma included in the nivolumab Expanded Access Program (EAP) in Italy. PloS one 23 29979712
1992 Distribution of the novel developmentally-regulated protein EAP-300 in the embryonic chick nervous system. Brain research. Developmental brain research 23 1600624
1991 Identification of an amino acid-regulated mRNA from rat liver as the mammalian equivalent of bacterial ribosomal protein L22. The Journal of biological chemistry 22 1894596
2019 Real-world data from the Portuguese Nivolumab Expanded Access Program (EAP) in previously treated Non Small Cell Lung Cancer (NSCLC). Pulmonology 21 31630986
2006 23S rRNA 2058A-->G alteration mediates ketolide resistance in combination with deletion in L22. Antimicrobial agents and chemotherapy 21 16923950
1995 Developmentally regulated neural protein EAP-300 is expressed by myocardium and cardiac neural crest during chick embryogenesis. Developmental dynamics : an official publication of the American Association of Anatomists 21 7647374
2021 Staphylococcus aureus Depends on Eap Proteins for Preventing Degradation of Its Phenol-Soluble Modulin Toxins by Neutrophil Serine Proteases. Frontiers in immunology 20 34552584
2020 Isolation and characterization of a marine bacterium Vibrio diabolicus strain L2-2 capable of biotransforming sulfonamides. Environmental research 20 32497873
2001 The equine herpesvirus 1 immediate-early protein interacts with EAP, a nucleolar-ribosomal protein. Virology 19 11145900
1995 Molecular characterization of EAP-300: a high molecular weight, embryonic polypeptide containing an amino acid repeat comprised of multiple leucine-zipper motifs. Brain research. Developmental brain research 19 7781165
2024 RPL22 is a tumor suppressor in MSI-high cancers and a splicing regulator of MDM4. Cell reports 18 39146182
2009 Cloning and characterization of 60S ribosomal protein L22 (RPL22) from Culex pipiens pallens. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 18 19298862
2008 The Staphyloccous aureus Eap protein activates expression of proinflammatory cytokines. Infection and immunity 18 18332207
2022 HA/CD44 Regulates the T Helper 1 Cells Differentiation by Activating Annexin A1/Akt/mTOR Signaling to Drive the Pathogenesis of EAP. Frontiers in immunology 17 35693826
2022 Ribosomal protein L22-like1 (RPL22L1) mediates sorafenib sensitivity via ERK in hepatocellular carcinoma. Cell death discovery 17 35973992
2004 Inability of L22 ribosomal protein alteration to increase macrolide MICs in the absence of efflux mechanism in Haemophilus influenzae HMC-S. The Journal of antimicrobial chemotherapy 17 15243030
2024 Knockdown of ribosomal protein L22-like 1 arrests the cell cycle and promotes apoptosis in colorectal cancer. CytoJournal 16 39737125
2021 RPL22 Overexpression Promotes Psoriasis-Like Lesion by Inducing Keratinocytes Abnormal Biological Behavior. Frontiers in immunology 16 34220863
2017 Evidence for multiple modes of neutrophil serine protease recognition by the EAP family of Staphylococcal innate immune evasion proteins. Protein science : a publication of the Protein Society 16 29114958
2015 Regulatory Roles of Rpl22 in Hematopoiesis: An Old Dog with New Tricks. Critical reviews in immunology 16 26853850
2014 L-22 enhances the invasiveness of endometrial stromal cells of adenomyosis in an autocrine manner. International journal of clinical and experimental pathology 16 25337217
2003 Quinupristin-dalfopristin resistance in Streptococcus pneumoniae: novel L22 ribosomal protein mutation in two clinical isolates from the SENTRY antimicrobial surveillance program. Antimicrobial agents and chemotherapy 16 12878545
2023 Resolvin D1 Attenuates Inflammation and Pelvic Pain Associated with EAP by Inhibiting Oxidative Stress and NLRP3 Inflammasome Activation via the Nrf2/HO-1 Pathway. Journal of inflammation research 14 37576154
2021 The lncRNA ADAMTS9-AS2 Regulates RPL22 to Modulate TNBC Progression via Controlling the TGF-β Signaling Pathway. Frontiers in oncology 14 34178640
2014 Interaction of ribosomal protein L22 with casein kinase 2α: a novel mechanism for understanding the biology of non-small cell lung cancer. Oncology reports 14 24840952
2013 Mutations in the Escherichia coli ribosomal protein L22 selectively suppress the expression of a secreted bacterial virulence factor. Journal of bacteriology 14 23625843
2002 Interaction of casein kinase II with ribosomal protein L22 of Drosophila melanogaster. Biochemical and biophysical research communications 14 12379220
1991 A small gene family in barley encodes ribosomal proteins homologous to yeast YL17 and L22 from archaebacteria, eubacteria, and chloroplasts. Current genetics 14 1913880
2020 Post-transcriptional regulation of C-C motif chemokine ligand 2 expression by ribosomal protein L22 during LPS-mediated inflammation. The FEBS journal 13 32383535
2016 Rpl22 is required for IME1 mRNA translation and meiotic induction in S. cerevisiae. Cell division 13 27478489
2014 Absence of DICER1, CTCF, RPL22, DNMT3A, TRRAP, IDH1 and IDH2 hotspot mutations in patients with various subtypes of ovarian carcinomas. Biomedical reports 13 25469243
2006 Intrinsic and selected resistance to antibiotics binding the ribosome: analyses of Brucella 23S rrn, L4, L22, EF-Tu1, EF-Tu2, efflux and phylogenetic implications. BMC microbiology 13 17014718
1994 A novel heparin-binding protein, HBp15, is identified as mammalian ribosomal protein L22. Biochemical and biophysical research communications 13 8135813

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