TET-mediated 5-methylcytosine oxidation in tRNA promotes translation.
TET-mediated 5-methylcytosine oxidation in tRNA promotes translation.
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DOI：
10.1074/jbc.ra120.014226
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Liu KF
中科院分区：
文献类型：
--
作者：
Shen H;Ontiveros RJ;Owens MC;Liu MY;Ghanty U;Kohli RM;Liu KF
10-11 易位 (TET) 家族酶对 DNA 中 5-甲基胞嘧啶 (5mC) 的氧化对于哺乳动物的基因调控是必不可少的。最近，有证据支持信使 RNA 中 TET 介导的 m5C 氧化的生物学功能。在这里，我们描述了 TET 介导的 m5C 氧化在转移 RNA (tRNA) 中的先前未表征的作用。我们发现 TET 介导的氧化产物 5-羟甲基胞嘧啶 (hm5C) 在细胞内的 tRNA 中特异性富集，并且在体外可以轻松观察到 TET2 对 tRNA 中 m5C 的氧化活性。我们进一步观察到，与野生型 mESC 相比，Tet2 KO 小鼠胚胎干细胞 (mESC) 中 tRNA 中的 hm5C 水平显着降低。相反，相对于未诱导的细胞，TET2 催化结构域的诱导表达导致 tRNA 中 hm5C 明显增加和 m5C 减少。引人注目的是，我们还表明 tRNA 中 TET2 介导的 m5C 氧化可促进体外翻译。这些结果表明 TET2 可能通过影响 tRNA 甲基化来影响翻译，并揭示了 TET 酶在调节中心法则的多个节点中的意想不到的作用。
Oxidation of 5-methylcytosine (5mC) in DNA by the ten-eleven translocation (TET) family of enzymes is indispensable for gene regulation in mammals. More recently, evidence has emerged to support a biological function for TET-mediated m5C oxidation in messenger RNA. Here, we describe a previously uncharacterized role of TET-mediated m5C oxidation in transfer RNA (tRNA). We found that the TET-mediated oxidation product 5-hydroxylmethylcytosine (hm5C) is specifically enriched in tRNA inside cells and that the oxidation activity of TET2 on m5C in tRNAs can be readily observed in vitro. We further observed that hm5C levels in tRNA were significantly decreased in Tet2 KO mouse embryonic stem cells (mESCs) in comparison with wild-type mESCs. Reciprocally, induced expression of the catalytic domain of TET2 led to an obvious increase in hm5C and a decrease in m5C in tRNAs relative to uninduced cells. Strikingly, we also show that TET2-mediated m5C oxidation in tRNA promotes translation in vitro. These results suggest TET2 may influence translation through impacting tRNA methylation and reveal an unexpected role for TET enzymes in regulating multiple nodes of the central dogma.