| RPL3 is a conserved component of the large 60S ribosomal subunit and belongs to the uL3 family of ribosomal proteins, where it occupies a central position adjacent to the peptidyl transferase center and contributes directly to the structural and functional integrity of the eukaryotic translation machinery. The protein adopts a globular core with extended “tentacle”-like regions that penetrate deeply into the large subunit rRNA, contacting helices near the peptidyl transferase center and the sarcin–ricin loop, and these contacts stabilize rRNA architecture required for accurate positioning and accommodation of aminoacyl‑tRNA and peptidyl‑tRNA during peptide bond formation. Within pre‑ribosomal particles and mature ribosomes, RPL3 acts as a structural constituent that supports 60S subunit assembly, 80S subunit joining, and maintenance of translational fidelity, and yeast mutational analyses highlight a functionally important region near a conserved histidine and tryptophan “W‑finger” whose perturbation alters peptidyl transferase activity, aa‑tRNA binding, and sensitivity to peptidyl transferase–targeting antibiotics. RPL3 also participates in late steps of pre‑40S maturation by promoting 20S pre‑rRNA cleavage at site D within 80S‑like quality control complexes that contain pre‑40S and mature 60S subunits and the initiation factor eIF5B/Fun12; integrity of the RPL3 W‑finger region is required for stimulation of eIF5B GTPase activity and for productive 18S rRNA 3′‑end processing that licenses pre‑40S subunits for translation. In human cells, RPL3 expression is subject to autoregulation through alternative splicing coupled to nonsense‑mediated decay, and the RPL3 protein can redistribute from ribosomes to the nucleus under ribosomal stress, where it interacts with factors that control p21 expression and cell‑cycle progression in p53‑independent contexts, indicating that RPL3 links ribosome biogenesis status to stress-responsive transcriptional programs. RPL3 expression and integrity are therefore important not only for bulk translation and ribosome assembly but also for ribosomal stress signaling, and dysregulation or mutation in RPL3 has been associated with altered sensitivity to chemotherapeutic agents and with tumor cell proliferation phenotypes. |
