RPL23A

RPL23A encodes uL23, a conserved structural protein of the 60S large ribosomal subunit that is essential for ribosome assembly and provides a functional docking platform at the ribosomal tunnel exit (PMID:8428950, PMID:17584789). Genetic complementation in yeast established that the ribosomal assembly role is conserved across species: the Drosophila ortholog substitutes for yeast L25 to support viability and proper 27S→25S rRNA processing (PMID:17584789). At the tunnel exit, uL23 serves as the contact point for ribosome-associated factors that act cotranslationally, including the signal recognition particle, which engages the intra-tunnel loop of uL23 via its signal-sequence-binding domain to scan translating ribosomes for substrate selection (PMID:28134917). Beyond its ribosomal role, RPL23A participates in p53 regulation through multiple routes: it binds RPL11 to restrain the RPL11–MDM2–p53 axis, such that loss of RPL23A releases RPL11 to inhibit MDM2 and drive p53 accumulation and apoptosis (PMID:34782045), and a native peptide derived from RPL23A (PDRL23A) competes with RPL26 to suppress p53 translation under hypoxic stress (PMID:34808368). RPL23A protein abundance is controlled by the E3 ubiquitin ligase HERC3, which directly binds RPL23A and catalyzes K48-linked polyubiquitination and proteasomal degradation through its HECT domain, thereby influencing the c-Myc/p21 axis and cell-cycle progression (PMID:35637966). Consistent with an essential cellular role, suppression of RPL23A expression is antiproliferative (PMID:9053844).

1. 1993 Medium

   Established RPL23A as a defined molecular entity — a conserved 60S large-subunit ribosomal protein — placing it within the L23 family before any functional dissection.

   Evidence cDNA sequencing and hybridization analysis of rat L23a with cross-species homology comparison

   PMID:8428950

   Open questions at the time

   • Sequence identity alone did not demonstrate ribosomal assembly function
   • No mechanistic role at the tunnel exit established
2. 1997 Medium

   Showed that reducing RPL23A has a direct antiproliferative consequence, linking the gene's expression to cell growth rather than being a passive structural component.

   Evidence Antisense knockdown in HeLa cells with colony formation assay; IFN-beta-dependent downregulation

   PMID:9053844

   Open questions at the time

   • Did not distinguish loss of ribosome function from extra-ribosomal signaling effects
   • Mechanism connecting RPL23A to proliferation unresolved
3. 2007 High

   Demonstrated that RPL23A's ribosomal assembly role is functionally conserved, settling that the protein is genuinely required for large-subunit biogenesis and rRNA maturation.

   Evidence Yeast chromosomal disruption/complementation with Drosophila L23a and pulse-chase rRNA processing

   PMID:17584789

   Open questions at the time

   • Reduced growth rate of the complemented strain indicates incomplete functional equivalence
   • Specific structural contacts within assembling ribosome not defined
4. 2017 High

   Defined a specific cotranslational targeting function for the uL23 tunnel-exit loop, showing it is the SRP docking site that enables early substrate scanning.

   Evidence In vivo crosslinking and mutational analysis of bacterial uL23–SRP contact

   PMID:28134917

   Open questions at the time

   • Demonstrated in bacterial system; eukaryotic RPL23A–SRP contact not directly shown
   • Does not address other tunnel-exit factor interactions
5. 2021 Medium

   Placed RPL23A in p53 control by two distinct routes — sequestering RPL11 to restrain MDM2-p53, and generating a peptide that competes with RPL26 to suppress p53 translation.

   Evidence Knockdown, co-IP and apoptosis assays in spermatogonia; intracellular peptidomics, co-IP and I/R rescue for PDRL23A

   PMID:34782045 PMID:34808368

   Open questions at the time

   • Each pathway shown in a single tissue context (germ cells; cardiomyocytes)
   • Stoichiometry and physiological balance between ribosomal vs free RPL23A pools unclear
6. 2022 High

   Identified the mechanism controlling RPL23A protein levels — HERC3-mediated K48 ubiquitination and degradation — and linked this turnover to c-Myc/p21 and cell-cycle control in cancer.

   Evidence Reciprocal Co-IP, GST-pulldown, in vivo ubiquitylation, cycloheximide chase, and rescue in colorectal cancer cells

   PMID:35637966

   Open questions at the time

   • How RPL23A regulates the c-Myc/p21 axis mechanistically not fully resolved
   • Whether degradation targets ribosomal vs extra-ribosomal RPL23A unknown
7. 2025 Medium

   Directly visualized uL23 as a dynamic docking site for the chaperone Trigger Factor selectively on translating ribosomes, refining the tunnel-exit factor recruitment model.

   Evidence High-speed atomic force microscopy and molecular dynamics on bacterial ribosome-nascent chain complexes (preprint)

   PMID:bio_10.1101_2025.05.16.654432

   Open questions at the time

   • Preprint, not peer-reviewed
   • Bacterial system; eukaryotic RPL23A–chaperone dynamics not shown

• How the ribosomal and extra-ribosomal (p53-regulatory) pools of RPL23A are partitioned and coordinated in human cells remains unresolved.
• No quantitative model of free vs ribosome-bound RPL23A
• Eukaryotic structural validation of tunnel-exit factor contacts lacking
• Integration of HERC3-controlled abundance with p53 pathway output undefined