Liu Fange, Clark Wesley, Luo Guanzheng, Wang Xiaoyun, Fu Ye, Wei Jiangbo, Wang Xiao, Hao Ziyang, Dai Qing, Zheng Guanqun, Ma Honghui, Han Dali, Evans Molly, Klungland Arne, Pan Tao, He Chuan
Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
Department of Biochemistry and Molecular Biology and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57(th) Street, Chicago, IL 60637, USA.
Cell. 2016 Oct 20;167(3):816-828.e16. doi: 10.1016/j.cell.2016.09.038. Epub 2016 Oct 13.
tRNA is a central component of protein synthesis and the cell signaling network. One salient feature of tRNA is its heavily modified status, which can critically impact its function. Here, we show that mammalian ALKBH1 is a tRNA demethylase. It mediates the demethylation of N-methyladenosine (mA) in tRNAs. The ALKBH1-catalyzed demethylation of the target tRNAs results in attenuated translation initiation and decreased usage of tRNAs in protein synthesis. This process is dynamic and responds to glucose availability to affect translation. Our results uncover reversible methylation of tRNA as a new mechanism of post-transcriptional gene expression regulation.
转运RNA(tRNA)是蛋白质合成和细胞信号网络的核心组成部分。tRNA的一个显著特征是其高度修饰状态,这可能会严重影响其功能。在此,我们表明哺乳动物的ALKBH1是一种tRNA去甲基化酶。它介导tRNA中N-甲基腺苷(mA)的去甲基化。ALKBH1催化的靶标tRNA去甲基化导致翻译起始减弱以及蛋白质合成中tRNA的使用减少。这个过程是动态的,并对葡萄糖可用性做出反应以影响翻译。我们的结果揭示了tRNA的可逆甲基化是转录后基因表达调控的一种新机制。