Affinage

RPL3

Large ribosomal subunit protein uL3 · UniProt P39023

Length
403 aa
Mass
46.1 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RPL3 (uL3) is a universally conserved structural protein of the large ribosomal subunit whose extended loops project into the peptidyl transferase center (PTC), where it organizes catalysis and acts as an allosteric switch coordinating elongation (PMID:9873002, PMID:26906928). Genetic and footprinting studies in yeast and bacteria place L3 at the sarcin/ricin and PTC regions, where it binds 23S/25S rRNA and modulates rRNA conformation up to ~100 Å from the protein, the basis of its role as the target of peptidyl transferase inhibitors (trichodermin, anisomycin, tiamulin) and of drug-resistance mutations (PMID:7017711, PMID:9873002, PMID:12936991, PMID:17194937). Its central extension reciprocally tunes eEF1A-stimulated aa-tRNA accommodation versus eEF2 binding, controls peptidyl transfer rate, and influences -1 frameshifting (PMID:17386264), and a correctly configured GTPase activation region is required for eIF5B-dependent 3'-end processing of 18S rRNA during ribosome maturation quality control (PMID:24603549). RPL3 carries a stoichiometric 3-methylhistidine modification at His-243 (yeast)/His-245 (human) installed by the Hpm1/METTL18 methyltransferase; this PTC mark slows ribosome traversal of tyrosine codons to permit co-translational folding and maintain proteostasis, and its loss alters pre-rRNA processing and codon-specific translation (PMID:20864530, PMID:26826131, PMID:33693809, PMID:35674491). RPL3 expression is autoregulated through hnRNP H1-, KHSRP-, and NPM-dependent alternative splicing of intron 3 that generates an NMD-targeted isoform (PMID:20100605, PMID:21705779). Beyond the ribosome, nucleolar/ribosomal stress induces accumulation of a ribosome-free form of RPL3 that functions in a p53-independent manner as a transcriptional regulator—repressing CBS, xCT (SLC7A11), and GST-α1 via Sp1, upregulating p21 to drive G1/S arrest or mitochondrial apoptosis, interacting with PARP-1 to suppress E2F1 and Cyclin D1, modulating NF-κB, and inhibiting cytoprotective autophagy (PMID:23255119, PMID:25473889, PMID:27385096, PMID:28273808, PMID:31659203, PMID:32244996). A tissue-specific paralog swap in which RPL3 replaces RPL3L in cardiomyocytes increases ribosome-mitochondria interactions and ATP production without changing translational efficiency (PMID:36882085).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1981 High

    Established the molecular identity of L3 and its position at the drug-sensitive catalytic core by showing the yeast TCM1/MAK8 gene encodes L3 and is the target of peptidyl transferase inhibitors.

    Evidence Yeast genetic complementation and in vitro protein synthesis assays with trichodermin-resistant transformants

    PMID:7017711

    Open questions at the time
    • Did not localize L3 within the ribosome structurally
    • Did not define the rRNA contacts mediating drug sensitivity
  2. 1982 High

    Revealed an unexpected requirement of L3 for maintenance of the M dsRNA killer genome, hinting at roles beyond canonical translation.

    Evidence Genetic cosegregation and complementation with dsRNA gel analysis of tcm1 mutants

    PMID:6750608

    Open questions at the time
    • Mechanism linking L3 function to dsRNA replication unresolved
    • Whether effect is direct or via translation defects unclear
  3. 1999 High

    Positioned L3 at the sarcin/ricin domain of large-subunit rRNA and identified it as a direct protein receptor for ribosome-inactivating toxins.

    Evidence Bacterial L3 rRNA footprinting/mutagenesis plus reciprocal co-IP and in vivo depurination assays with pokeweed antiviral protein in yeast

    PMID:9873002 PMID:9920941

    Open questions at the time
    • Structural model of L3-rRNA interface not yet resolved
    • Cross-species transferability of bacterial contacts inferred, not shown in human
  4. 2003 High

    Mapped resistance-conferring L3 substitutions to the PTC cleft, demonstrating L3 loops directly shape the drug- and substrate-binding pocket.

    Evidence E. coli and Brachyspira resistance mutant selection, complementation, sequencing, and chemical footprinting of tiamulin binding

    PMID:12936991 PMID:15554969

    Open questions at the time
    • Did not resolve atomic structure of altered PTC
    • Allosteric versus direct steric contribution not separated
  5. 2007 High

    Defined L3 as an allosteric switch coupling elongation factor binding, tRNA accommodation, and peptidyl transfer, transforming it from a passive scaffold to an active regulator of elongation.

    Evidence Yeast genetics, tRNA/EF binding biochemistry, chemical probing, frameshifting reporters, and DMS protection of mutant ribosomes

    PMID:17194937 PMID:17386264

    Open questions at the time
    • Atomic basis of long-range allostery not structurally resolved at this stage
    • Physiological consequences of frameshifting modulation unquantified
  6. 2010 High

    Identified L3 as the substrate of a histidine methyltransferase and established autoregulation of its own expression through alternative splicing-coupled NMD.

    Evidence Mass spectrometry, radiolabeling, and HPM1 deletion for the 3-methylhistidine modification; EMSA, splicing assays, and knockdown of hnRNP H1 for autoregulation

    PMID:20100605 PMID:20864530

    Open questions at the time
    • Functional consequence of His methylation not yet defined
    • Whether splicing autoregulation is conserved beyond the studied system unclear
  7. 2011 Medium

    Expanded the splicing-autoregulation circuit by showing KHSRP and NPM cooperate with hnRNP H1 on rpL3 intron 3.

    Evidence Co-IP and RNA immunoprecipitation of the hnRNP H1/KHSRP/NPM complex with rpL3 RNA

    PMID:21705779

    Open questions at the time
    • Co-IP/RIP from single lab without reciprocal orthogonal validation
    • Stoichiometry and assembly order of the complex unresolved
  8. 2014 High

    Connected L3 conformation to ribosome biogenesis quality control, showing its GTPase activation region is required for eIF5B-dependent 18S rRNA 3'-end maturation, and introduced ribosome-free RPL3 as a stress-induced effector.

    Evidence rpl3 allele genetics, pre-rRNA processing and particle purification with eIF5B GTPase assays; ribosome fractionation and knockdown in p53-null cancer cells under 5-FU/L-OHP

    PMID:24603549 PMID:25473889

    Open questions at the time
    • Mechanism by which L3 conformation gates eIF5B activity incomplete
    • How ribosome-free pool is generated/stabilized not defined
  9. 2016 Medium

    Built the extraribosomal program of ribosome-free RPL3: it represses CBS, drives p21 and mitochondrial apoptosis via Sp1/ERK/MDM2, and modulates NF-κB, while His methylation was shown to enforce elongation fidelity.

    Evidence Ribosome fractionation, co-IP (RPL3-CBS), Sp1/p21 reporters, mitochondrial fractionation and apoptosis assays in p53-null/mutant cancer cells; rpl3-H243A mutagenesis with translation fidelity assays

    PMID:26636733 PMID:26826131 PMID:27385096 PMID:27924828

    Open questions at the time
    • Extraribosomal transcriptional findings largely from a single lab
    • Direct DNA binding versus Sp1-tethering not fully separated
  10. 2016 High

    Provided the structural basis for L3's catalytic role, showing the W255C mutation disrupts the A-site of the PTC and that anisomycin restores a wild-type-like configuration.

    Evidence X-ray crystallography of vacant and anisomycin-bound mutant yeast ribosomes

    PMID:26906928

    Open questions at the time
    • Structure of the methylated PTC not captured here
    • Dynamics of the allosteric switch not resolved by static structures
  11. 2017 Medium

    Extended ribosome-free RPL3 to redox and drug-resistance control by demonstrating direct promoter binding to repress xCT and GST-α1, regulating ROS/glutathione independently of Nrf2.

    Evidence ChIP, luciferase reporters, ROS/glutathione measurement, and knockdown in p53-mutated MDR lung cancer cells

    PMID:28273808

    Open questions at the time
    • ChIP from single lab; co-occupancy with Sp1 not resolved
    • In vivo relevance to tumor drug resistance not established
  12. 2019 Medium

    Added PARP-1 as a direct partner of ribosome-free RPL3 in suppressing E2F1 and Cyclin D1 to gate the G1/S transition under nucleolar stress.

    Evidence Co-IP (uL3-PARP-1), E2F1 promoter reporters, Western blotting, and qRT-PCR

    PMID:31659203

    Open questions at the time
    • Single-lab co-IP without reciprocal structural validation
    • Direct versus indirect E2F1 regulation not separated
  13. 2020 Medium

    Implicated RPL3 as a suppressor of cytoprotective autophagy, linking its loss to chemoresistance.

    Evidence RNA-Seq, confocal imaging of autophagy markers, chloroquine treatment, and stable knockdown in colon cancer cells

    PMID:32244996

    Open questions at the time
    • Direct molecular target in autophagy machinery unidentified
    • Single-lab functional study
  14. 2021 High

    Confirmed METTL18 as the human RPL3 His-245 methyltransferase and showed the modification governs pre-rRNA processing, polysome formation, and codon-specific translation.

    Evidence RPL3 interactomics, in vitro methylation with recombinant METTL18, METTL18-KO mass spectrometry, polysome and ribosome profiling

    PMID:33693809

    Open questions at the time
    • Codon-level mechanism not yet structurally explained at this stage
    • Physiological proteostasis consequence not directly demonstrated here
  15. 2021 Medium

    Identified DUOX2 as a regulator of RPL3 stability via ubiquitination, linking RPL3 to PI3K-AKT-dependent invasion in colorectal cancer.

    Evidence Co-IP, ubiquitination assay, RPL3 overexpression rescue, and NGS in colorectal cancer cells

    PMID:32531052

    Open questions at the time
    • Ubiquitination site and E3 ligase not defined
    • Single Co-IP with limited mechanistic depth
  16. 2022 High

    Resolved the proteostatic function of His-245 methylation, showing it slows ribosomes at Tyr codons to permit co-translational folding and prevent aggregation of Tyr-rich proteins.

    Evidence In vitro methylation, mass spectrometry, Ribo-seq, in vitro translation, cryo-EM of modified vs unmodified ribosomes, and aggregation assays

    PMID:35674491

    Open questions at the time
    • Regulation of METTL18 activity in vivo unclear
    • Disease relevance of methylation loss not established
  17. 2023 High

    Demonstrated functional non-equivalence of RPL3 versus its paralog RPL3L, with RPL3-containing ribosomes increasing ribosome-mitochondria coupling and ATP production in cardiomyocytes.

    Evidence Rpl3l-KO mouse, Ribo-seq, Nano-TRAP ribosome pulldown sequencing, ATP and mitochondria-ribosome interaction assays

    PMID:36882085

    Open questions at the time
    • Molecular basis of differential mitochondrial coupling unresolved
    • Whether RPL3/RPL3L exchange occurs physiologically in human heart not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the ribosomal and extraribosomal lives of RPL3 are mechanistically partitioned—and whether the extraribosomal transcriptional functions generalize beyond the originating cancer-cell systems—remains open.
  • No structural model of ribosome-free RPL3 bound to Sp1, PARP-1, or promoter DNA
  • Cues triggering ribosome release of RPL3 undefined
  • Human in vivo relevance of cancer-cell extraribosomal findings untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003723 RNA binding 3 GO:0005198 structural molecule activity 2 GO:0098772 molecular function regulator activity 2 GO:0003677 DNA binding 1
Localization
GO:0005840 ribosome 4 GO:0005634 nucleus 3 GO:0005730 nucleolus 2 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
CBSDUOX2HNRNP H1HPM1METTL18NPMPARP-1SP1
Complex memberships
hnRNP H1/KHSRP/NPM rpL3 splicing regulatory complexlarge ribosomal subunit (60S/50S)peptidyl transferase center

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1981 The yeast TCM1/MAK8 gene encodes ribosomal protein L3, and mutations in this gene confer resistance to trichodermin and related drugs (verrucarin A, anisomycin). Polyribosomes from transformed cells are resistant to trichodermin in an in vitro protein synthesis assay, establishing L3 as the target of these peptidyl transferase inhibitors. Yeast transformation with recombinant plasmids, genetic complementation, in vitro protein synthesis assay, subcloning Proceedings of the National Academy of Sciences of the United States of America High 7017711
1982 Ribosomal protein L3 (encoded by MAK8/TCM1) is required for replication and maintenance of the M double-stranded RNA (killer) genome in S. cerevisiae; tcm1 mutations cause loss of M1/M2 dsRNA but not L dsRNA. Genetic cosegregation analysis, complementation tests, dsRNA gel analysis Proceedings of the National Academy of Sciences of the United States of America High 6750608
1999 Pokeweed antiviral protein (PAP) binds directly to ribosomal protein L3 to access ribosomes. Wild-type L3 is required for PAP to bind to ribosomes and depurinate the 25S rRNA alpha-sarcin loop; the mak8-1 allele of L3 confers resistance to PAP by preventing ribosome-associated L3 from interacting with PAP. Co-immunoprecipitation (in vitro), yeast genetics (mak8-1 chromosomal mutant), in vivo depurination assay The Journal of biological chemistry High 9920941
1999 L3 (bacterial) binds directly to the sarcin/ricin domain of 23S rRNA (positions A-2632, A-2634, A-2635, A-2675, A-2726, A-2733, A-2749, A-2750), and cooperative binding of L3 and L6 together protects additional nucleotides in the sarcin/ricin loop, indicating that L3 is located near the peptidyl transferase center and modulates the conformation of this functional RNA domain. Gel shift, filter binding, DMS chemical footprinting of 23S rRNA, site-directed mutagenesis of rRNA The Journal of biological chemistry Medium 9873002
2001 Active-site cleft residues of PAP (positions 69-70 and 90-92) mediate high-affinity binding to ribosomal protein L3; PAP mutants with alanine substitutions at these positions show >150-fold reduced affinity for both ribosomes and recombinant L3 protein as measured by surface plasmon resonance. Co-immunoprecipitation, surface plasmon resonance biosensor, site-directed mutagenesis of PAP active-site cleft residues Biochemistry High 11478877
2003 A single mutation in E. coli ribosomal protein L3 (Asn149Asp, A445G in gene) causes resistance to the peptidyl transferase inhibitor tiamulin by reducing drug binding to the ribosome. Chemical footprinting showed reduced tiamulin binding to mutant ribosomes; the L3 loop points into the peptidyl transferase cleft. Selection of resistant mutants, complementation experiments, sequencing of transductants, chemical footprinting Antimicrobial agents and chemotherapy High 12936991
2004 Mutations in ribosomal protein L3 (amino acid positions 148 and 149) in Brachyspira spp. cause reduced tiamulin susceptibility by reducing drug binding to ribosomal subunits at the peptidyl transferase centre, as shown by chemical footprinting. Sequencing of resistance mutants, chemical footprinting of ribosomal subunits Molecular microbiology Medium 15554969
2004 Mutant forms of yeast L3 result in ribosomes with increased affinities for both aminoacyl- and peptidyl-tRNAs, decreased peptidyltransferase activity, and altered rRNA structure up to 100 Å from the mutation site (detected by DMS protection), supporting an allosteric model of ribosome function. In vivo DMS dimethylsulfate protection, peptidyltransferase activity assay, tRNA binding assays, drug resistance phenotyping RNA biology Medium 17194937
2007 The central extension of yeast ribosomal protein L3 functions as an allosteric switch coordinating elongation factor binding: mutations in this region alter the reciprocal relationship between eEF-1A-stimulated aa-tRNA binding and eEF2 binding, inhibit peptidyltransferase activity, stimulate programmed -1 ribosomal frameshifting, and confer resistance to the A-site inhibitor anisomycin by opening the aa-tRNA accommodation corridor. Molecular genetics, biochemical tRNA/EF binding assays, chemical probing, molecular modeling, frameshifting reporter assays Molecular cell High 17386264
2010 Yeast ribosomal protein Rpl3 is stoichiometrically monomethylated at histidine 243 (producing 3-methylhistidine) by the YIL110W/Hpm1 methyltransferase (a seven-β-strand methyltransferase). Deletion of HPM1 abolishes this modification and leads to phenotypes including abnormal interactions between Rpl3 and 25S rRNA. Top-down and bottom-up mass spectrometry, radiolabeling with S-adenosyl-[methyl-³H]methionine, cation-exchange chromatography, TLC, deletion strain analysis of 37 methyltransferases The Journal of biological chemistry High 20864530
2010 hnRNP H1 acts as a trans-acting splicing factor that binds directly to G-rich elements (G3 and G6) within intron 3 of the rpL3 pre-mRNA, promoting selection of the alternative splice site and generating a PTC-containing NMD-targeted isoform, thereby mediating rpL3 autoregulation of its own expression. RNA EMSA, co-immunoprecipitation (in vivo RNP), siRNA knockdown and overexpression of hnRNP H1, site-directed mutagenesis of G-rich elements, in vivo splicing assays Biochimica et biophysica acta High 20100605
2011 NPM and KHSRP are additional regulators of rpL3 alternative splicing-NMD autoregulation. hnRNP H1, KHSRP, and NPM form a complex that associates with rpL3 and intron 3 RNA in vivo, and protein-protein and RNA-protein interactions among these factors control the alternative splicing of rpL3 pre-mRNA. Co-immunoprecipitation, RNA immunoprecipitation, protein/RNA interaction assays Nucleic acids research Medium 21705779
2012 Ribosome-free rpL3 regulates cell cycle and apoptosis in a p53-independent manner by directly interacting with Sp1 to upregulate p21 (waf1/cip1) transcription; elevated p21 levels lead to either G1/S arrest or mitochondrial apoptosis depending on intracellular p21 concentration. Depletion of p21 abrogates both effects. rpL3 overexpression/depletion, luciferase reporter assays, co-immunoprecipitation (rpL3-Sp1 interaction), cell cycle analysis, apoptosis assays in p53-null cells Cell cycle (Georgetown, Tex.) Medium 23255119
2014 The rpl3[W255C] allele impairs cytoplasmic maturation of 20S pre-rRNA to 18S rRNA. Pre-40S particles from rpl3[W255C] cells form translation-competent 80S ribosomes, but the GTPase activity of eIF5B (Fun12) fails to stimulate 20S pre-rRNA processing in particles purified from these cells, indicating that the correct conformation of the GTPase activation region of L3 is required for eIF5B-dependent 3' end processing of 18S rRNA during a quality control step. Genetic analysis (rpl3 allele), pre-rRNA processing assays, ribosome particle purification, eIF5B GTPase activity assay, translation inhibitor experiments PLoS genetics High 24603549
2014 In p53-null cancer cells, nucleolar stress induced by 5-FU and L-OHP causes upregulation of rpL3 and its accumulation as a ribosome-free form; ribosome-free rpL3 acts as a critical regulator of cell cycle, apoptosis, and DNA repair by modulating p21 expression. Silencing of rpL3 abolishes cytotoxic effects of these drugs. siRNA knockdown of rpL3, Western blotting for ribosome-free rpL3 fractionation, cell cycle and apoptosis assays, p21 expression analysis Oncotarget Medium 25473889
2016 5-FU treatment causes rpL3 to accumulate as ribosome-free form in p53-null colon cancer cells; free rpL3 represses CBS transcription via Sp1 and reduces CBS protein stability through direct rpL3-CBS association, which also triggers CBS translocation into mitochondria leading to mitochondrial apoptosis (increased Bax/Bcl-2, cytochrome c release, caspase activation). Ribosome fractionation, co-immunoprecipitation (rpL3-CBS), luciferase reporter assays (Sp1-CBS promoter), mitochondrial fractionation, apoptosis assays Oncotarget Medium 27385096
2016 Actinomycin D-induced ribosomal stress causes accumulation of ribosome-free rpL3, which regulates p21 expression at transcriptional and post-translational levels through a mechanism involving ERK1/2 and MDM2. rpL3 silencing abolishes Act D cytotoxic effects; rpL3 overexpression enhances Act D-mediated inhibition of cell migration. siRNA knockdown, ribosome fractionation, Western blotting, cell migration assays, kinase pathway analysis Cell cycle (Georgetown, Tex.) Medium 26636733
2016 In p53-mutated lung cancer cells (Calu-6), 5-FU-induced ribosome-free rpL3 represses CBS transcription and reduces CBS protein stability, and also prevents NFκB nuclear translocation through IκB-α upregulation, enhancing apoptosis and inhibiting cell migration/invasion. siRNA knockdown, luciferase reporter assays, Western blotting, cell migration and invasion assays Scientific reports Medium 27924828
2016 Methylation of yeast Rpl3 at histidine 243 by Hpm1 promotes translational elongation fidelity; rpl3-H243A mutant cells (mimicking unmethylated state) accumulate 35S and 23S pre-rRNA precursors and display defects in translation elongation accuracy, demonstrating that histidine methylation of Rpl3 at the basic thumb region is required for accurate translation elongation. Site-directed mutagenesis (rpl3-H243A), pre-rRNA processing analysis, translational fidelity assays, ribosomal subunit analysis RNA (New York, N.Y.) High 26826131
2016 Crystal structure of the yeast uL3 W255C mutant ribosome reveals disruption of the A-site side of the peptidyl transferase center; high concentrations of anisomycin restore a WT-like PTC configuration, explaining the resistance mechanism. The structure demonstrates that uL3 is structurally essential for optimal catalytic organization of the PTC. X-ray crystallography of vacant mutant ribosome and anisomycin-bound mutant ribosome Journal of molecular biology High 26906928
2017 uL3 (rpL3) controls multidrug resistance in p53-mutated lung cancer cells by acting as a transcriptional repressor of xCT (SLC7A11) and GST-α1, thereby regulating cellular redox status (ROS levels, glutathione content, glutamate release, cystine uptake) independently of Nrf2. ChIP experiments confirmed direct uL3 binding to these gene promoters. Chromatin immunoprecipitation (ChIP), luciferase reporter assays, ROS/glutathione measurement, siRNA knockdown of uL3, MDR cell line characterization International journal of molecular sciences Medium 28273808
2019 Ribosome-free uL3 physically interacts with PARP-1 to negatively regulate E2F1 transcriptional activity, and also reduces Cyclin D1 mRNA and protein levels, thereby controlling G1/S transition in cancer cells under nucleolar stress. Protein/protein co-immunoprecipitation (uL3-PARP-1), luciferase reporter assays (E2F1 promoter), Western blotting, qRT-PCR Scientific reports Medium 31659203
2020 uL3 acts as an inhibitory factor of autophagy in colon cancer cells; absence of uL3 is associated with increased autophagic flux and chemoresistance. Transcriptome analysis and Western blotting/confocal microscopy demonstrated that uL3 depletion activates cytoprotective autophagy, while uL3 presence suppresses it. Transcriptome analysis (RNA-Seq), confocal microscopy, Western blotting for autophagy markers, chloroquine treatment, uL3 stable knockdown cell line International journal of molecular sciences Medium 32244996
2021 Human METTL18 is the histidine-specific methyltransferase responsible for 3-methylhistidine modification of RPL3 at His-245 (τ-position). METTL18 KO cells lack this modification, and METTL18 accumulates in nucleoli. Loss of METTL18-mediated RPL3 methylation causes altered pre-rRNA processing, decreased polysome formation, and codon-specific changes in mRNA translation. RPL3 interactomics (MS), in vitro methylation assay with recombinant METTL18, quantitative mass spectrometry of METTL18 KO cells, polysome profiling, ribosome profiling, pre-rRNA processing analysis Nucleic acids research High 33693809
2022 METTL18-mediated His-245 3-methylhistidine modification of RPL3 specifically slows ribosome traversal on Tyr codons, allowing proper folding of synthesized proteins; unmodified RPL3 leads to aggregation of Tyr-rich proteins. Structural comparison of modified and unmodified ribosomes showed stoichiometric modification at the PTC. In vitro methylation assay with methyl donor analog, quantitative mass spectrometry, genome-wide ribosome profiling (Ribo-seq), in vitro translation assay, cryo-EM structural comparison, protein aggregation assays eLife High 35674491
2023 In cardiomyocytes, RPL3L-containing ribosomes are the default form; upon RPL3L depletion, RPL3 is upregulated and substitutes for RPL3L. RPL3-containing (vs. RPL3L-containing) ribosomes show increased ribosome-mitochondria interactions, leading to increased ATP levels and altered mitochondrial activity, without modulation of translational efficiency or ribosome affinity for specific transcripts. Rpl3l knockout mouse, ribosome profiling (Ribo-seq), ribosome pulldown coupled to nanopore sequencing (Nano-TRAP), ATP measurement, mitochondria-ribosome interaction assays Nucleic acids research High 36882085
2021 DUOX2 interacts with RPL3 (uL3) and regulates its ubiquitination status (stability); overexpression of RPL3 reverses the enhanced invasion and migration ability conferred by DUOX2 in colorectal cancer cells. DUOX2 knockdown affects a large number of genes enriched in the PI3K-AKT pathway in part through RPL3. Immunoprecipitation (DUOX2-RPL3 interaction), ubiquitination assay, RPL3 overexpression rescue, invasion/migration assays, next-generation sequencing Carcinogenesis Medium 32531052

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution. The EMBO journal 217 9233788
1998 The L3 loop: a structural motif determining specific interactions between SMAD proteins and TGF-beta receptors. The EMBO journal 208 9463378
2001 Human natural killer cells with polyclonal lectin and immunoglobulinlike receptors develop from single hematopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2. Blood 164 11468170
1991 The open reading frames UL3, UL4, UL10, and UL16 are dispensable for the replication of herpes simplex virus 1 in cell culture. Journal of virology 161 1846207
2010 AFP, AFP-L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC. Journal of gastroenterology 156 20625772
2011 The Expansion of mtDNA Haplogroup L3 within and out of Africa. Molecular biology and evolution 151 22096215
1981 Cloning of yeast gene for trichodermin resistance and ribosomal protein L3. Proceedings of the National Academy of Sciences of the United States of America 141 7017711
1998 Cleavage of the C-terminus of NEDD8 by UCH-L3. Biochemical and biophysical research communications 137 9790970
2004 RNA interference targeting cathepsin L and Z-like cysteine proteases of Onchocerca volvulus confirmed their essential function during L3 molting. Molecular and biochemical parasitology 133 15555728
2017 Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma. Medicine 120 28296720
1983 Nucleotide sequence of the tcml gene (ribosomal protein L3) of Saccharomyces cerevisiae. Journal of bacteriology 99 6305925
1995 The Capsicum L3 gene-mediated resistance against the tobamoviruses is elicited by the coat protein. Virology 96 7778282
2004 Mutations in ribosomal protein L3 and 23S ribosomal RNA at the peptidyl transferase centre are associated with reduced susceptibility to tiamulin in Brachyspira spp. isolates. Molecular microbiology 93 15554969
2006 High expression of ubiquitin carboxy-terminal hydrolase-L1 and -L3 mRNA predicts early recurrence in patients with invasive breast cancer. Cancer science 88 16734731
1999 Pokeweed antiviral protein accesses ribosomes by binding to L3. The Journal of biological chemistry 88 9920941
2007 The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel. The Journal of biological chemistry 87 17967898
2001 Loss of Uch-L1 and Uch-L3 leads to neurodegeneration, posterior paralysis and dysphagia. Human molecular genetics 81 11555633
2004 The LIM homeobox gene, L3/Lhx8, is necessary for proper development of basal forebrain cholinergic neurons. The European journal of neuroscience 79 15217369
2016 rpL3 promotes the apoptosis of p53 mutated lung cancer cells by down-regulating CBS and NFκB upon 5-FU treatment. Scientific reports 74 27924828
2010 A novel 3-methylhistidine modification of yeast ribosomal protein Rpl3 is dependent upon the YIL110W methyltransferase. The Journal of biological chemistry 73 20864530
2016 5-FU targets rpL3 to induce mitochondrial apoptosis via cystathionine-β-synthase in colon cancer cells lacking p53. Oncotarget 70 27385096
2012 Human rpL3 induces G₁/S arrest or apoptosis by modulating p21 (waf1/cip1) levels in a p53-independent manner. Cell cycle (Georgetown, Tex.) 70 23255119
2008 Glycomic analysis of alpha-fetoprotein L3 in hepatoma cell lines and hepatocellular carcinoma patients. Journal of proteome research 66 18479159
2000 Expression and functional analysis of Uch-L3 during mouse development. Molecular and cellular biology 65 10713173
2007 Ribosomal protein L3: gatekeeper to the A site. Molecular cell 63 17386264
2015 Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma. OncoTargets and therapy 61 26770061
1982 Ribosomal protein L3 is involved in replication or maintenance of the killer double-stranded RNA genome of Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 61 6750608
2016 Expression of Muscle-Specific Ribosomal Protein L3-Like Impairs Myotube Growth. Journal of cellular physiology 59 26684695
2023 Apolipoprotein L3 enhances CD8+ T cell antitumor immunity of colorectal cancer by promoting LDHA-mediated ferroptosis. International journal of biological sciences 57 36923931
2003 Resistance to the peptidyl transferase inhibitor tiamulin caused by mutation of ribosomal protein l3. Antimicrobial agents and chemotherapy 56 12936991
2001 Translocation activity of C-terminal domain of pestivirus Erns and ribotoxin L3 loop. The Journal of biological chemistry 55 11673454
2016 Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53. Cell cycle (Georgetown, Tex.) 54 26636733
1992 Identification and transcriptional analyses of the UL3 and UL4 genes of equine herpesvirus 1, homologs of the ICP27 and glycoprotein K genes of herpes simplex virus. Journal of virology 54 1323700
2005 L3/Lhx8 is involved in the determination of cholinergic or GABAergic cell fate. Journal of neurochemistry 53 16000160
2021 Human METTL18 is a histidine-specific methyltransferase that targets RPL3 and affects ribosome biogenesis and function. Nucleic acids research 50 33693809
2014 Final pre-40S maturation depends on the functional integrity of the 60S subunit ribosomal protein L3. PLoS genetics 50 24603549
1993 A 3' coterminal gene cluster in pseudorabies virus contains herpes simplex virus UL1, UL2, and UL3 gene homologs and a unique UL3.5 open reading frame. Journal of virology 49 8396663
2014 Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5-FU and L-OHP. Oncotarget 48 25473889
1996 Identification and characterization of the pseudorabies virus UL3.5 protein, which is involved in virus egress. Journal of virology 47 8648685
2016 Enhancement of 5-FU sensitivity by the proapoptotic rpL3 gene in p53 null colon cancer cells through combined polymer nanoparticles. Oncotarget 46 27835895
2003 L-3,4-Dihydroxyphenylalanine as a neurotransmitter candidate in the central nervous system. Pharmacology & therapeutics 45 12559386
2017 Role of uL3 in Multidrug Resistance in p53-Mutated Lung Cancer Cells. International journal of molecular sciences 43 28273808
2023 Dynamic interplay between RPL3- and RPL3L-containing ribosomes modulates mitochondrial activity in the mammalian heart. Nucleic acids research 42 36882085
2019 Proteome profiling of L3 and L4 Anisakis simplex development stages by TMT-based quantitative proteomics. Journal of proteomics 40 30978463
1996 A novel ribosomal protein L3-like gene (RPL3L) maps to the autosomal dominant polycystic kidney disease gene region. Genomics 40 8921388
2015 Mutations in the bacterial ribosomal protein l3 and their association with antibiotic resistance. Antimicrobial agents and chemotherapy 39 25845869
2018 Molecular characterization and functional activity of CXCL8_L3 in large yellow croaker Larimichthys crocea. Fish & shellfish immunology 37 29367006
2014 Ubiquitin C-terminal hydrolase-L3 regulates EMT process and cancer metastasis in prostate cell lines. Biochemical and biophysical research communications 37 25194810
2018 A null variant in the apolipoprotein L3 gene is associated with non-diabetic nephropathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 36 28339911
2009 Ubiquitin carboxyl-terminal hydrolase l3 promotes insulin signaling and adipogenesis. Endocrinology 36 19837878
1995 Identification and transcriptional analysis of a 3'-coterminal gene cluster containing UL1, UL2, UL3, and UL3.5 open reading frames of bovine herpesvirus-1. Virology 35 7483276
2022 METTL18-mediated histidine methylation of RPL3 modulates translation elongation for proteostasis maintenance. eLife 34 35674491
2011 Autoregulatory circuit of human rpL3 expression requires hnRNP H1, NPM and KHSRP. Nucleic acids research 34 21705779
2010 hnRNP H1 and intronic G runs in the splicing control of the human rpL3 gene. Biochimica et biophysica acta 33 20100605
2007 L3/Lhx8 is a pivotal factor for cholinergic differentiation of murine embryonic stem cells. Cell death and differentiation 33 17318222
1999 The binding site for UCH-L3 on ubiquitin: mutagenesis and NMR studies on the complex between ubiquitin and UCH-L3. Journal of molecular biology 33 10518943
2020 Role of uL3 in the Crosstalk between Nucleolar Stress and Autophagy in Colon Cancer Cells. International journal of molecular sciences 32 32244996
2019 Ribosomal protein uL3 targets E2F1 and Cyclin D1 in cancer cell response to nucleolar stress. Scientific reports 32 31659203
2004 Ribosomal protein L3: influence on ribosome structure and function. RNA biology 32 17194937
2022 Diagnostic Performance of AFP, AFP-L3, or PIVKA-II for Hepatitis C Virus-Associated Hepatocellular Carcinoma: A Multicenter Analysis. Journal of clinical medicine 30 36079006
2014 Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 30 25209179
2004 Silencing of ribosomal protein L3 genes in N. tabacum reveals coordinate expression and significant alterations in plant growth, development and ribosome biogenesis. The Plant journal : for cell and molecular biology 30 15200640
2021 DUOX2 promotes the progression of colorectal cancer cells by regulating the AKT pathway and interacting with RPL3. Carcinogenesis 29 32531052
2016 Methylation of yeast ribosomal protein Rpl3 promotes translational elongation fidelity. RNA (New York, N.Y.) 29 26826131
2009 Transcriptomes and pathways associated with infectivity, survival and immunogenicity in Brugia malayi L3. BMC genomics 29 19527522
2006 Oncolytic viruses derived from the gamma34.5-deleted herpes simplex virus recombinant R3616 encode a truncated UL3 protein. Molecular therapy : the journal of the American Society of Gene Therapy 29 16574492
2020 S-Adenosyl-l-Methionine Overcomes uL3-Mediated Drug Resistance in p53 Deleted Colon Cancer Cells. International journal of molecular sciences 28 33374288
2018 Diverse serotonin actions of vilazodone reduce l-3,4-dihidroxyphenylalanine-induced dyskinesia in hemi-parkinsonian rats. Movement disorders : official journal of the Movement Disorder Society 28 30485908
2008 Ubiquitin dimers control the hydrolase activity of UCH-L3. Neurochemistry international 28 19154770
1999 Mammalian reovirus L3 gene sequences and evidence for a distinct amino-terminal region of the lambda1 protein. Virology 28 10329567
2000 Structural relationships and sialylation among meningococcal L1, L8, and L3,7 lipooligosaccharide serotypes. The Journal of biological chemistry 27 10734124
2016 Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects. European journal of pharmacology 26 26852952
1997 IMP-L3, A 20-hydroxyecdysone-responsive gene encodes Drosophila lactate dehydrogenase: structural characterization and developmental studies. Developmental genetics 26 9094207
2001 Active center cleft residues of pokeweed antiviral protein mediate its high-affinity binding to the ribosomal protein L3. Biochemistry 25 11478877
2019 Propriospinal Neurons of L3-L4 Segments Involved in Control of the Rat External Urethral Sphincter. Neuroscience 24 31785359
1999 Interaction of the sarcin/ricin domain of 23 S ribosomal RNA with proteins L3 and L6. The Journal of biological chemistry 24 9873002
2011 Ubiquitin C-terminal hydrolase-L3 regulates Smad1 ubiquitination and osteoblast differentiation. FEBS letters 23 21453705
2020 uL3 Mediated Nucleolar Stress Pathway as a New Mechanism of Action of Antiproliferative G-quadruplex TBA Derivatives in Colon Cancer Cells. Biomolecules 22 32290083
2004 Toxin-dependent utilization of engineered ribosomal protein L3 limits trichothecene resistance in transgenic plants. Plant biotechnology journal 22 17134394
1998 Escherichia coli ribosomal protein L3 stimulates the helicase activity of the Bacillus stearothermophilus PcrA helicase. Nucleic acids research 22 9580688
2020 Overexpression of ubiquitin-conjugating enzyme E2 L3 in hepatocellular carcinoma potentiates apoptosis evasion by inhibiting the GSK3β/p65 pathway. Cancer letters 21 32268166
2016 Crystal Structures of the uL3 Mutant Ribosome: Illustration of the Importance of Ribosomal Proteins for Translation Efficiency. Journal of molecular biology 21 26906928
2023 Apolipoproteins L1 and L3 control mitochondrial membrane dynamics. Cell reports 20 38041817
1993 The herpes simplex virus type 2 UL3 open reading frame encodes a nuclear localizing phosphoprotein. Virology 20 8337818
2002 Comparison of the expression patterns of two LIM-homeodomain genes, Lhx6 and L3/Lhx8, in the developing palate. Orthodontics & craniofacial research 19 12086327
2013 Characterization and differential expression of cathepsin L3 alleles from Fasciola hepatica. Molecular and biochemical parasitology 18 23770026
1999 Nucleolar localization of the UL3 protein of herpes simplex virus type 2. The Journal of general virology 18 10466815
2017 MicroRNA Expression Profiling of Pancreatic Cancer Cell Line L3.6p1 Following B7-H4 Knockdown. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 17 29145206
2005 The conserved poxvirus L3 virion protein is required for transcription of vaccinia virus early genes. Journal of virology 17 16282472
2021 UCH-L3 structure and function: Insights about a promising drug target. European journal of medicinal chemistry 16 34752952
2007 Relevance of the interaction between alphaherpesvirus UL3.5 and UL48 proteins for virion maturation and neuroinvasion. Journal of virology 16 17581981
2024 Bone marrow mesenchymal stem cells-derived exosomal lncRNA GAS5 mitigates heart failure by inhibiting UL3/Hippo pathway-mediated ferroptosis. European journal of medical research 15 38812041
2023 Combining β-Carotene with 5-FU via Polymeric Nanoparticles as a Novel Therapeutic Strategy to Overcome uL3-Mediated Chemoresistance in p53-Deleted Colorectal Cancer Cells. Molecular pharmaceutics 15 36976623
2022 Evaluation of the Efficacy of Enterococcus faecium L3 as a Feed Probiotic Additive in Chicken. Probiotics and antimicrobial proteins 15 35904731
2003 cDNA cloning, expression and characterization of an allergenic L3 ribosomal protein of Aspergillus fumigatus. Clinical and experimental immunology 15 12974759
2023 Integrated metabolomics and peptidomics to delineate characteristic metabolites in milk fermented with novel Lactiplantibacillus plantarum L3. Food chemistry: X 14 37397209
2018 Carriers of mitochondrial DNA macrohaplogroup L3 basal lineages migrated back to Africa from Asia around 70,000 years ago. BMC evolutionary biology 14 29921229
2018 Analysis of serum alpha-fetoprotein (AFP) and AFP-L3 levels by protein microarray. The Journal of international medical research 14 30111217
2016 Comparison of AFP-L3 and p53 Antigen Concentration with Alpha-Fetoprotein as Serum Markers for Hepatocellular Carcinoma. Clinical laboratory 14 27468575
1997 Functional complementation of UL3.5-negative pseudorabies virus by the bovine herpesvirus 1 UL3.5 homolog. Journal of virology 13 9343253

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