Proteostasis regulation through ribosome quality control and no‐go‐decay

Abstract

Cell functionality relies on the existing pool of proteins and their folding into functional conformations. This is achieved through the regulation of protein synthesis, which requires error‐free mRNAs and ribosomes. Ribosomes are quality control hubs for mRNAs and proteins. Problems during translation elongation slow down the decoding rate, leading to ribosome halting and the eventual collision with the next ribosome. Collided ribosomes form a specific disome structure recognized and solved by ribosome quality control (RQC) mechanisms. RQC pathways orchestrate the degradation of the problematic mRNA by no‐go decay and the truncated nascent peptide, the repression of translation initiation, and the recycling of the stalled ribosomes. All these events maintain protein homeostasis and return valuable ribosomes to translation. As such, cell homeostasis and function are maintained at the mRNA level by preventing the production of aberrant or unnecessary proteins. It is becoming evident that the crosstalk between RQC and the protein homeostasis network is vital for cell function, as the absence of RQC components leads to the activation of stress response and neurodegenerative diseases. Here, we review the molecular events of RQC discovered through well‐designed stalling reporters. Given the impact of RQC in proteostasis, we discuss the relevance of identifying endogenous mRNA regulated by RQC and their preservation in stress conditions.This article is categorized under: RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms Translation > Regulation

Transcriptional profile of ribosome-associated quality control components and their associated phenotypes in mammalian cells

“…It acts as a scaffolding protein capable of interacting with numerous partners and recruiting translation regulators. RACK1 provides an interface for recognition by ZNF598, allowing the separation of ribosomal subunits and the downstream recruitment of RQC 48 , 49 . Additionally, the ASC-1 complex, formed by ASCC1, ASCC2, and ASCC3 (helicase), separates the ribosomal subunits in an ATP-, ZNF598-, and ubiquitin-dependent reaction 24 , 50 .…”