國(guó)立過(guò)敏與傳染病研究所病毒病實(shí)驗(yàn)室,、遺傳性學(xué)系、生物與化學(xué)系,、Ben May研究所,，芝加哥大學(xué)醫(yī)學(xué)院的科學(xué)家們?cè)诘鞍邹D(zhuǎn)錄翻譯的研究過(guò)程中發(fā)現(xiàn)了新的機(jī)制，相關(guān)成果文章Innate immune and chemically triggered oxidative stress modifies translational fidelity公布在最新一期的Nature雜志上,。
要使細(xì)胞發(fā)揮正常的功能,，每一個(gè)細(xì)胞器、每一種轉(zhuǎn)錄翻譯的蛋白都必須保證不出錯(cuò),。蛋白翻譯的保真度（Translational fidelity）是維持細(xì)胞功能和形態(tài)正常的關(guān)鍵,，在這個(gè)過(guò)程中，準(zhǔn)確地將tRNA翻譯成蛋白是最核心的步驟,。
然而,，現(xiàn)象的研究發(fā)現(xiàn)，一種氨基酸的翻譯過(guò)程中出現(xiàn)了10%的出錯(cuò)率,，令人驚訝的是這種出錯(cuò)的出現(xiàn)在因自體免疫或是病毒細(xì)菌刺激的氧化應(yīng)激情況下,。
用HeLa細(xì)胞所做研究表明，蛋白合成中所用蛋氨酸殘跡的約1%被氨?；闪嗽诮炭茣?shū)上被認(rèn)為不正確的tRNA,。令人吃驚的是，當(dāng)細(xì)胞通過(guò)病毒感染或用病毒或細(xì)菌類Toll-樣受體配體處理而處于壓力之下時(shí),，由蛋氨酸被錯(cuò)誤氨?；傻膖RNA比例顯著增加。
用其他氨基酸所做試驗(yàn)表明,，該現(xiàn)象僅限于蛋氨酸,，而且因?yàn)榈鞍彼釟堐E已知保護(hù)蛋白不受活性氧分子所造成損傷的影響，所以一種可能性是,，蛋氨酸誤氨?；菍?duì)細(xì)胞壓力的一種自然的保護(hù)性反應(yīng)。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 462, 522-526 (26 November 2009) | doi:10.1038/nature08576
Innate immune and chemically triggered oxidative stress modifies translational fidelity
Nir Netzer1,6, Jeffrey M. Goodenbour2,6, Alexandre David1, Kimberly A. Dittmar3, Richard B. Jones4, Jeffrey R. Schneider5, David Boone5, Eva M. Eves4, Marsha R. Rosner4, James S. Gibbs1, Alan Embry1, Brian Dolan1, Suman Das1, Heather D. Hickman1, Peter Berglund1, Jack R. Bennink1, Jonathan W. Yewdell1,6 & Tao Pan3,6
1 Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA
2 Department of Human Genetics,
3 Department of Biochemistry and Molecular Biology,
4 Ben May Institute,
5 Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
6 These authors contributed equally to this work.
Correspondence to: Jonathan W. Yewdell1,6Tao Pan3,6 Correspondence and requests for materials should be addressed to J.W.Y. or T.P.
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 couplings1, 2. The accuracy of tRNA aminoacylation in vivo is uncertain, however, and might be considerably lower3, 4, 5, 6. 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 damage7, 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.
