新《Nature》发现蛋白翻译错误率达10%

【字体: 时间:2009年11月27日 来源:生物通

编辑推荐:

  生物通报道,国立过敏与传染病研究所病毒病实验室、遗传性学系、生物与化学系、Ben May研究所,芝加哥大学医学院的科学家们在蛋白转录翻译的研究过程中发现了新的机制,相关成果文章Innate immune and chemically triggered oxidative stress modifies translational fidelity公布在最新一期的Nature杂志上。

  

生物通报道,国立过敏与传染病研究所病毒病实验室、遗传性学系、生物与化学系、Ben May研究所,芝加哥大学医学院的科学家们在蛋白转录翻译的研究过程中发现了新的机制,相关成果文章Innate immune and chemically triggered oxidative stress modifies translational fidelity公布在最新一期的Nature杂志上。

 

要使细胞发挥正常的功能,每一个细胞器、每一种转录翻译的蛋白都必须保证不出错。蛋白翻译的保真度(Translational fidelity)是维持细胞功能和形态正常的关键,在这个过程中,准确地将tRNA翻译成蛋白是最核心的步骤。

 

然而,现象的研究发现,一种氨基酸的翻译过程中出现了10%的出错率,令人惊讶的是这种出错的出现在因自体免疫或是病毒细菌刺激的氧化应激情况下。

 

HeLa细胞所做研究表明,蛋白合成中所用蛋氨酸残迹的约1%被氨酰化成了在教科书上被认为不正确的tRNA。令人吃惊的是,当细胞通过病毒感染或用病毒或细菌类Toll-样受体配体处理而处于压力之下时,由蛋氨酸被错误氨酰化而生成的tRNA比例显著增加。

 

用其他氨基酸所做试验表明,该现象仅限于蛋氨酸,而且因为蛋氨酸残迹已知保护蛋白不受活性氧分子所造成损伤的影响,所以一种可能性是,蛋氨酸误氨酰化是对细胞压力的一种自然的保护性反应。

(生物通 小茜)

 

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

 

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA

Department of Human Genetics,

Department of Biochemistry and Molecular Biology,

Ben May Institute,

Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA

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. (Email: jyewdell@nih.gov) or T.P. (Email: taopan@uchicago.edu).

 

Abstract

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.

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