ALKBH1-Mediated tRNA Demethylation Regulates Translation.

ALKBH1-Mediated tRNA Demethylation Regulates Translation.
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DOI:
10.1016/j.cell.2016.09.038
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发表时间:
2016-10-20
期刊:
影响因子:
64.5
通讯作者:
He, Chuan
He, Chuan
中科院分区:
生物学1区
文献类型:
--
作者:
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

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转移RNA(TRNA)是蛋白质合成和细胞信号网络的重要组成部分。TRNA的一个显著特征是其状态被严重修改,这可能严重影响其功能。在这里,我们证明了哺乳动物的ALKBH1是一种tRNA去甲基酶。它介导tRNAs中N1-甲基腺苷(M1a)的去甲基化。ALKBH1催化的靶tRNAs去甲基化导致翻译起始减弱,并减少了它们在蛋白质合成中的使用。这个过程是动态的,并对葡萄糖的可获得性做出反应,以影响翻译。我们的结果揭示了tRNA可逆甲基化是转录后基因表达的一种新的调控机制。可逆的tRNA甲基化有助于翻译对营养可获得性的反应。
Transfer RNA (tRNA) is a central component of protein synthesis and 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 N1-methyladenosine (m1A) in tRNAs. The ALKBH1-catalyzed demethylation of the target tRNAs results in attenuated translation initiation and their decreased usage 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 regulatory mechanism of post-transcriptional gene expression. Reversible tRNA methylation helps translation respond to nutrient availability.
DOI: 10.1016/j.molcel.2007.09.021
发表时间: 2007-12-14
期刊: MOLECULAR CELL
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