The central role of translation elongation in response to stress

Abstract

Protein synthesis is essential to support homeostasis, and thus, must be highly regulated during cellular response to harmful environments. All stages of translation are susceptible to regulation under stress, however, the mechanisms involved in translation regulation beyond initiation have only begun to be elucidated. Methodological advances enabled critical discoveries on the control of translation elongation, highlighting its important role in translation repression and the synthesis of stress-response proteins. In this article, we discuss recent findings on mechanisms of elongation control mediated by ribosome pausing and collisions and the availability of tRNAs and elongation factors. We also discuss how elongation intersects with distinct modes of translation control, further supporting cellular viability and gene expression reprogramming. Finally, we highlight how several of these pathways are reversibly regulated, emphasizing the dynamics of translation control during stress-response progression. A comprehensive understanding of translation regulation under stress will produce fundamental knowledge of protein dynamics while opening new avenues and strategies to overcome dysregulated protein production and cellular sensitivity to stress.

Absolute calibration of ribosome profiling assesses the dynamics of ribosomal flux on transcripts

“…Although many studies concluded that the translation initiation dominantly determines the protein synthesis rate in growing cells 59,75–82,84 . On the other hand, under stressed conditions, the perturbed elongation rate determines the protein production rate 85–87 . Importantly, our method provides a useful tool to understand kinetic relationships between translation initiation and elongation in wide arrays of cellular situations.…”

ROS-induced translational regulation—through spatiotemporal differences in codon recognition—is a key driver of brown adipogenesis

“…The fact that codons can influence translation implies that the elongation step must be affected. Oxidative stress can slow down translation elongation through various means 37 . However, in this study, initiation is still the rate-limiting step because the translation bias we detected from sequencing was reproduced in the luciferase reporter assays, i.e.…”

Context specific ubiquitin modification of ribosomes regulates translation under oxidative stress

“…While genomic and transcriptomic induction of stress-specific gene expression programs have been extensively investigated (Mascarenhas et al, 2008;Taymaz-Nikerel et al, 2016), many aspects of the induction at the proteomic level remain unclear. In response to many forms of stress, cells suppress global translation while simultaneously inducing the production of selective stress-response proteins (Barros et al, 2023;Shenton et al, 2006). This global suppression is crucial to prevent damage to newly synthesized proteins, prevent toxic gain-of-functions, and minimize extraneous energy expenditure on non-essential proteins (Holcik & Sonenberg, 2005).…”