TRMT2A is a novel cell cycle regulator that suppresses cell proliferation
TRMT2A is a novel cell cycle regulator that suppresses cell proliferation
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DOI：
10.1016/j.bbrc.2018.11.104
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发表时间：
2019-01-08
影响因子：
3.1
通讯作者：
Takahashi, Satoru
中科院分区：
文献类型：
--
作者：
Chang, Yu-Hsin;Nishimura, Susumu;Takahashi, Satoru
在转运RNA（transfer RNA，tRNA）成熟过程中，可以在转录后的特定核苷酸位置引入多种化学修饰。5-甲基尿苷（Methyluridine，m（5）U）是从真细菌到真核生物最常见和最保守的修饰之一。虽然大肠杆菌中的TrmA蛋白和酿酒酵母中的Trm 2 p蛋白（它们负责tRNA上54位尿嘧啶（m（5）U 54）的5-甲基化）已被很好地表征，但哺乳动物物种中U 54甲基化负责酶的生物学功能仍在很大程度上未被探索。在这里，我们表明，哺乳动物tRNA甲基转移酶2同源物A（TRMT 2A）蛋白窝藏在N-末端和保守的尿嘧啶-C5-甲基转移酶结构域的TrmA家族的C-末端的RNA识别基序。TRMT 2A主要定位于HeLa细胞的细胞核。TRMT 2A过表达的细胞表现出细胞增殖降低和DNA含量改变，而TRMT 2A缺陷的细胞表现出生长增加。因此，我们的研究结果揭示了TRMT 2A对细胞增殖和细胞周期控制的抑制作用，为TRMT 2A是哺乳动物细胞周期调节因子的候选者提供了证据。(C)2018作者爱思唯尔公司出版
During the maturation of transfer RNA (tRNA), a variety of chemical modifications can be introduced at specific nucleotide positions post-transcriptionally. 5-Methyluridine (m(5)U) is one of the most common and conserved modifications from eubacteria to eukaryotes. Although TrmA protein in Escherichia coli and Trm2p protein in Saccharomyces cerevisiae, which are responsible for the 5-methylation of uracil at position 54 (m(5)U54) on tRNA, are well characterized, the biological function of the U54 methylation responsible enzyme in mammalian species remains largely unexplored. Here, we show that the mammalian tRNA methyltransferase 2 homolog A (TRMT2A) protein harbors an RNA recognition motif in the N-terminus and the conserved uracil-C5-methyltransferase domain of the TrmA family in the C-terminus. TRMT2A predominantly localizes to the nucleus in HeLa cells. TRMT2A-overexpressing cells display decreased cell proliferation and altered DNA content, while TRMT2A-deficient cells exhibit increased growth. Thus, our results reveal the inhibitory role of TRMT2A on cell proliferation and cell cycle control, providing evidence that TRMT2A is a candidate cell cycle regulator in mammals. (C) 2018 The Authors. Published by Elsevier Inc.