1. Relocalization of Translation Termination and Ribosome Recycling Factors to Stress Granules Coincides with Elevated Stop-Codon Readthrough and Reinitiation Rates upon Oxidative Stress.
- Author
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Makeeva DS, Riggs CL, Burakov AV, Ivanov PA, Kushchenko AS, Bykov DA, Popenko VI, Prassolov VS, Ivanov PV, and Dmitriev SE
- Subjects
- Animals, Codon, Terminator, Ribosomes metabolism, Stress Granules, Protein Biosynthesis, RNA, Messenger genetics, RNA, Messenger metabolism, Oxidative Stress, Mammals metabolism, Arsenites pharmacology, Arsenites metabolism
- Abstract
Upon oxidative stress, mammalian cells rapidly reprogram their translation. This is accompanied by the formation of stress granules (SGs), cytoplasmic ribonucleoprotein condensates containing untranslated mRNA molecules, RNA-binding proteins, 40S ribosomal subunits, and a set of translation initiation factors. Here we show that arsenite-induced stress causes a dramatic increase in the stop-codon readthrough rate and significantly elevates translation reinitiation levels on uORF-containing and bicistronic mRNAs. We also report the recruitment of translation termination factors eRF1 and eRF3, as well as ribosome recycling and translation reinitiation factors ABCE1, eIF2D, MCT-1, and DENR to SGs upon arsenite treatment. Localization of these factors to SGs may contribute to a rapid resumption of mRNA translation after stress relief and SG disassembly. It may also suggest the presence of post-termination, recycling, or reinitiation complexes in SGs. This new layer of translational control under stress conditions, relying on the altered spatial distribution of translation factors between cellular compartments, is discussed.
- Published
- 2023
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