TET2 chemically modifies tRNAs and regulates tRNA fragment levels.

TET2 chemically modifies tRNAs and regulates tRNA fragment levels.
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TET2 对 tRNA 进行化学修饰并调节 tRNA 片段水平

DOI:
10.1038/s41594-020-00526-w
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发表时间:
2021-01
影响因子:
16.8
通讯作者:
Bonasio R
Bonasio R
中科院分区:
生物学1区
文献类型:
--
作者:
He C;Bozler J;Janssen KA;Wilusz JE;Garcia BA;Schorn AJ;Bonasio R

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TET 2蛋白(TET 2)氧化DNA中的5-甲基胞嘧啶,也可以结合RNA;然而,体内TET 2-RNA相互作用的靶点和功能尚未完全了解。使用严格的亲和标签在Tet 2基因座,我们纯化和测序TET 2交联的RNA从小鼠胚胎干细胞(mESC),发现了一个高富集的tRNA。用5-羟甲基胞嘧啶(hm 5C)抗体进行RNA免疫沉淀,回收了与细胞中TET 2结合的tRNA重叠的tRNA。质谱分析表明,TET 2是必要的和足够的沉积的hm 5C修饰的tRNA。TET 2基因敲除影响了几个小的非编码RNA的水平,这些RNA来自于通过hm 5C免疫沉淀富集的TET 2结合的tRNA。因此,我们的研究结果表明TET 2在促进5-甲基胞嘧啶转化为tRNA上的hm 5C和调节不同类型的tRNA片段的加工或稳定性方面具有新的功能。
The Ten-eleven Translocation 2 (TET2) protein, which oxidizes 5-methylcytosine in DNA, can also bind RNA; however, the targets and function of TET2–RNA interactions in vivo are not fully understood. Using stringent affinity tags introduced at the Tet2 locus, we purified and sequenced TET2-crosslinked RNAs from mouse embryonic stem cells (mESCs) and found a high enrichment for tRNAs. RNA immunoprecipitation with an antibody against 5-hydroxymethylcytosine (hm5C) recovered tRNAs that overlapped with those bound to TET2 in cells. Mass spectrometry analyses revealed that TET2 is necessary and sufficient for the deposition of the hm5C modification on tRNA. Tet2 knockout in mESCs affected the levels of several small noncoding RNAs originating from TET2-bound tRNAs that were enriched by hm5C immunoprecipitation. Thus, our results suggest a novel function of TET2 in promoting the conversion of 5-methylcytosine to hm5C on tRNA and regulating the processing or stability of different classes of tRNA fragments.
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