Ribosome dynamics and mRNA turnover, a complex relationship under constant cellular scrutiny

Abstract

Eukaryotic gene expression is closely regulated by translation and turnover of mRNAs. Recent advances highlight the importance of translation in the control of mRNA degradation, both for aberrant and apparently normal mRNAs.During translation, the information contained in mRNAs is decoded by ribosomes, one codon at a time, and tRNAs, by specifically recognizing codons, translate the nucleotide code into amino acids. Such a decoding step does not process regularly, with various obstacles that can hinder ribosome progression, then leading to ribosome stalling or collisions. The progression of ribosomes is constantly monitored by the cell which has evolved several translationdependent mRNA surveillance pathways, including nonsense-mediated decay (NMD), no-go decay (NGD), and non-stop decay (NSD), to degrade certain problematic mRNAs and the incomplete protein products. Recent progress in sequencing and ribosome profiling has made it possible to discover new mechanisms controlling ribosome dynamics, with numerous crosstalks between translation and mRNA decay. We discuss here various translation features critical for mRNA decay, with particular focus on current insights from the complexity of the genetic code and also the emerging role for the ribosome as a regulatory hub orchestrating mRNA decay, quality control, and stress signaling. Even if the interplay between mRNA translation and degradation is no longer to be demonstrated, a better understanding of their precise coordination is worthy of further investigation.

Newly synthesized mRNA escapes translational repression during the acute phase of the mammalian unfolded protein response

“…Physiological processes such as mitosis or stress conditions that involve transient inhibition of protein synthesis are also characterized by transient mRNA stabilization (Ross 1997; Tanenbaum et al 2015; Kawai et al 2004; Majumder et al 2012). The mechanisms for this regulation are still obscure; however, they are likely to involve the suggested loss of interaction between the stabilized mRNAs and factors of the degradation machinery when their translation is inhibited (Heck and Wilusz 2018; Morris et al 2021). This would agree with more current reports of mRNA degradation occurring co-translationally (Pelechano et al 2015).…”

Shaping the Innate Immune Response Through Post-Transcriptional Regulation of Gene Expression Mediated by RNA-Binding Proteins

“…However, this model has been challenged in the past few years by studies indicating that P-bodies can be sites of mRNA storage and "triage" before resuming translation or being degraded (258,259). Furthermore, growing evidence points to a close link between mRNA translation and degradation, which can occur simultaneously, outside of P-bodies (249,(260)(261)(262)(263). Finally, endonuclease-associated mRNA decay can also occur, initiated by internal cleavage and followed by bidirectional exonuclease degradation (264).…”

Catalytic activities, molecular connections, and biological functions of plant RNA exosome complexes

“…Yet, the exosome has a well investigated role in so-called RNA quality control (RQC) pathways that make a considerable contribution to the physiological regulation of mRNA levels. A hallmark of these pathways is the stalling or collision of ribosomes at specific features ( D’Orazio and Green, 2021 ; Morris et al, 2021 ). No-go decay (NGD) removes mRNAs with rare codons or strong secondary structures ( Harigaya and Parker, 2010 ).…”