RRC ID 89782
Author Hirata M, Fujino M, Ichihara K, Tang R, Narita M, Iwasaki W, Shiraishi C, Shiraishi T, Hatano A, Suzuki T, Abe T, Takami T, Mishiro-Sato E, Toyoda A, Matsumoto M, Tanaka Y, Ito T, Inada T, Nakayama KI, Yokoyama T, Matsumoto A.
Title RPL41 stabilizes ribosome dynamics and supports long-protein homeostasis in mammals.
Journal Nucleic Acids Res
Abstract Ribosomal protein L41 (RPL41 or eL41) is the smallest ribosomal protein and forms the eukaryote-specific bridge, eB14, near the decoding center; however, its role in mammalian translation remains unclear. In this study, we established RPL41-deficient models of human HEK293T cells and mice to define its function. Cryo-electron microscopy revealed that RPL41 constrains intersubunit conformational dynamics without inducing major local static rearrangements. Loss of RPL41 altered A-site dynamics, slowed elongation, modestly increased amino acid misincorporation, and modestly enhanced readthrough of collision-inducing reporter sequences. Quantitative proteomic analysis suggested that these translational defects compromise long-protein homeostasis, as evidenced by increased insolubility and reduced abundance of long proteins. In vivo, Rpl41-/- mice were viable but exhibited growth retardation and decreased abundance of long proteins in tissues. Our findings reveal a conserved role for RPL41 in maintaining ribosome dynamics and translational fidelity, indicating that RPL41 supports ribosome function and long-protein homeostasis in mammals.
Volume 54(15)
Published 2026-8-10
DOI 10.1093/nar/gkag797
PII 8760021
PMID 42613035
PMC PMC13485352
MeSH Animals HEK293 Cells Homeostasis Humans Mice Mice, Knockout Protein Biosynthesis* Proteostasis* Ribosomal Proteins* / chemistry Ribosomal Proteins* / genetics Ribosomal Proteins* / metabolism Ribosomal Proteins* / physiology Ribosomes* / chemistry Ribosomes* / metabolism Ribosomes* / ultrastructure
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Total number of mentions 9
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Resource
Human and Animal Cells 293T(RCB2202)