Control of translation elongation in health and disease.

Autor:	Knight JRP; Beatson Institute for Cancer Research, Glasgow G61 1BD, UK., Garland G; MRC Toxicology Unit, University of Cambridge, Lancaster Road, Leicester LE1 9HN, UK., Pöyry T; MRC Toxicology Unit, University of Cambridge, Lancaster Road, Leicester LE1 9HN, UK., Mead E; School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK., Vlahov N; Beatson Institute for Cancer Research, Glasgow G61 1BD, UK., Sfakianos A; MRC Toxicology Unit, University of Cambridge, Lancaster Road, Leicester LE1 9HN, UK., Grosso S; MRC Toxicology Unit, University of Cambridge, Lancaster Road, Leicester LE1 9HN, UK., De-Lima-Hedayioglu F; School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK., Mallucci GR; UK Dementia Research Institute at the University of Cambridge and Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0XY, UK., von der Haar T; School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK., Smales CM; School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK., Sansom OJ; Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.; Institute of Cancer Sciences, University of Glasgow, Glasgow, G61 1QH, UK., Willis AE; MRC Toxicology Unit, University of Cambridge, Lancaster Road, Leicester LE1 9HN, UK aew80@mrc-tox.cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2020 Mar 26; Vol. 13 (3). Date of Electronic Publication: 2020 Mar 26.
DOI:	10.1242/dmm.043208
Abstrakt:	Regulation of protein synthesis makes a major contribution to post-transcriptional control pathways. During disease, or under stress, cells initiate processes to reprogramme protein synthesis and thus orchestrate the appropriate cellular response. Recent data show that the elongation stage of protein synthesis is a key regulatory node for translational control in health and disease. There is a complex set of factors that individually affect the overall rate of elongation and, for the most part, these influence either transfer RNA (tRNA)- and eukaryotic elongation factor 1A (eEF1A)-dependent codon decoding, and/or elongation factor 2 (eEF2)-dependent ribosome translocation along the mRNA. Decoding speeds depend on the relative abundance of each tRNA, the cognate:near-cognate tRNA ratios and the degree of tRNA modification, whereas eEF2-dependent ribosome translocation is negatively regulated by phosphorylation on threonine-56 by eEF2 kinase. Additional factors that contribute to the control of the elongation rate include epigenetic modification of the mRNA, coding sequence variation and the expression of eIF5A, which stimulates peptide bond formation between proline residues. Importantly, dysregulation of elongation control is central to disease mechanisms in both tumorigenesis and neurodegeneration, making the individual key steps in this process attractive therapeutic targets. Here, we discuss the relative contribution of individual components of the translational apparatus (e.g. tRNAs, elongation factors and their modifiers) to the overall control of translation elongation and how their dysregulation contributes towards disease processes. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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