Dedicated chaperones coordinate co-translational regulation of ribosomal protein production with ribosome assembly to preserve proteostasis

eLife

Laurent Falquet¹  Guillaume Murat²  Michael Stumpe²  Benjamin Pillet²  Dieter Kressler²  Alfonso Méndez-Godoy²  Sébastien Favre² 

[1] Metabolomics and Proteomics Platform, Department of Biology, University of Fribourg, Fribourg, Switzerland;Department of Biology, University of Fribourg, Fribourg, Switzerland;

关键词: ribosome biogenesis;    protein aggregation;    protein homeostasis;    Ccr4-Not complex;    mRNA degradation;    yeast genetics;   

DOI  :  10.7554/eLife.74255

来源: DOAJ

【 摘 要 】

The biogenesis of eukaryotic ribosomes involves the ordered assembly of around 80 ribosomal proteins. Supplying equimolar amounts of assembly-competent ribosomal proteins is complicated by their aggregation propensity and the spatial separation of their location of synthesis and pre-ribosome incorporation. Recent evidence has highlighted that dedicated chaperones protect individual, unassembled ribosomal proteins on their path to the pre-ribosomal assembly site. Here, we show that the co-translational recognition of Rpl3 and Rpl4 by their respective dedicated chaperone, Rrb1 or Acl4, reduces the degradation of the encoding RPL3 and RPL4 mRNAs in the yeast Saccharomyces cerevisiae. In both cases, negative regulation of mRNA levels occurs when the availability of the dedicated chaperone is limited and the nascent ribosomal protein is instead accessible to a regulatory machinery consisting of the nascent-polypeptide-associated complex and the Caf130-associated Ccr4-Not complex. Notably, deregulated expression of Rpl3 and Rpl4 leads to their massive aggregation and a perturbation of overall proteostasis in cells lacking the E3 ubiquitin ligase Tom1. Taken together, we have uncovered an unprecedented regulatory mechanism that adjusts the de novo synthesis of Rpl3 and Rpl4 to their actual consumption during ribosome assembly and, thereby, protects cells from the potentially detrimental effects of their surplus production.

【 授权许可】

Unknown