Publication Date:
2009-11-27
Description:
Translational fidelity, essential for protein and cell function, requires accurate transfer RNA (tRNA) aminoacylation. Purified aminoacyl-tRNA synthetases exhibit a fidelity of one error per 10,000 to 100,000 couplings. The accuracy of tRNA aminoacylation in vivo is uncertain, however, and might be considerably lower. Here we show that in mammalian cells, approximately 1% of methionine (Met) residues used in protein synthesis are aminoacylated to non-methionyl-tRNAs. Remarkably, Met-misacylation increases up to tenfold upon exposing cells to live or non-infectious viruses, toll-like receptor ligands or chemically induced oxidative stress. Met is misacylated to specific non-methionyl-tRNA families, and these Met-misacylated tRNAs are used in translation. Met-misacylation is blocked by an inhibitor of cellular oxidases, implicating reactive oxygen species (ROS) as the misacylation trigger. Among six amino acids tested, tRNA misacylation occurs exclusively with Met. As Met residues are known to protect proteins against ROS-mediated damage, we propose that Met-misacylation functions adaptively to increase Met incorporation into proteins to protect cells against oxidative stress. In demonstrating an unexpected conditional aspect of decoding mRNA, our findings illustrate the importance of considering alternative iterations of the genetic code.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785853/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785853/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Netzer, Nir -- Goodenbour, Jeffrey M -- David, Alexandre -- Dittmar, Kimberly A -- Jones, Richard B -- Schneider, Jeffrey R -- Boone, David -- Eves, Eva M -- Rosner, Marsha R -- Gibbs, James S -- Embry, Alan -- Dolan, Brian -- Das, Suman -- Hickman, Heather D -- Berglund, Peter -- Bennink, Jack R -- Yewdell, Jonathan W -- Pan, Tao -- Z01 AI000542-20/Intramural NIH HHS/ -- Z01 AI000653-16/Intramural NIH HHS/ -- Z01 AI000658-16/Intramural NIH HHS/ -- Z01 AI001014-01/Intramural NIH HHS/ -- England -- Nature. 2009 Nov 26;462(7272):522-6. doi: 10.1038/nature08576.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940929" target="_blank"〉PubMed〈/a〉
Keywords:
Adenoviridae/physiology
;
Animals
;
Genetic Code
;
HeLa Cells
;
Humans
;
*Immunity, Innate
;
Ligands
;
Methionine/genetics/*metabolism
;
Mice
;
Models, Genetic
;
NADPH Oxidase/metabolism
;
Orthomyxoviridae/physiology
;
Oxidative Stress/drug effects/genetics/*physiology
;
RNA, Transfer, Met/genetics/metabolism
;
Reactive Oxygen Species/metabolism
;
Substrate Specificity
;
Toll-Like Receptors/immunology/metabolism
;
Transfer RNA Aminoacylation/drug effects/*physiology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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