Hydroxylation and translational adaptation to stress: some answers lie beyond the STOP codon

Abstract

Regulation of protein synthesis contributes to maintenance of homeostasis and adaptation to environmental changes. mRNA translation is controlled at various levels including initiation, elongation and termination, through post-transcriptional/translational modifications of components of the protein synthesis machinery. Recently, protein and RNA hydroxylation have emerged as important enzymatic modifications of tRNAs, elongation and termination factors, as well as ribosomal proteins. These modifications enable a correct STOP codon recognition, ensuring translational fidelity. Recent studies are starting to show that STOP codon read-through is related to the ability of the cell to cope with different types of stress, such as oxidative and chemical insults, while correlations between defects in hydroxylation of protein synthesis components and STOP codon read-through are beginning to emerge. In this review we will discuss our current knowledge of protein synthesis regulation through hydroxylation of components of the translation machinery, with special focus on STOP codon recognition. We speculate on the possibility that programmed STOP codon read-through, modulated by hydroxylation of components of the protein synthesis machinery, is part of a concerted cellular response to stress.

Biogenesis and iron-dependency of ribosomal RNA hydroxylation

“…Hydroxylation of biological molecules is a fundamental enzymatic reaction involved in various biological events ( 72 , 73 ). In the context of the epitranscriptome, hydroxylation is a major modification that modulates RNA functions ( 73 ) and as such is involved in several tRNA modifications ( 34 , 74 – 77 ).…”

The non-stop decay mRNA surveillance pathway is required for oxidative stress tolerance

“…We therefore considered that conditions which promote nonsense suppression might cause read-through of multiple mRNA stop codons effectively generating NSD substrates. Oxidative stress conditions are known to alter translation efficiency and for example, have been shown to promote misreading including translational read-through of stop codons (9,33,34). The possible mechanisms underlying this increase in read-through during oxidative stress conditions are largely unknown.…”

Oxidative Damage of Mussels Living in Seawater Enriched with Trace Metals, from the Viewpoint of Proteins Expression and Modification

“…Considering that translation factors under stress not only undergo changes in their expression or oxidation status but are also regulated by several modifications, such as phosphorylation, hydroxylation, and acetylation among others, reviewed by [57], our study was expanded using antibodies against a series of translation factors that follow an orchestrating quick adaptation to metal environmental challenges that mussels may face. Representative Western blots are given in Figure 5.…”