Methylation by NSun2 Represses the Levels and Function of MicroRNA 125b
Methylation by NSun2 Represses the Levels and Function of MicroRNA 125b
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DOI：
10.1128/mcb.00243-14
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发表时间：
2014-07
影响因子：
5.3
通讯作者：
Shuai Yuan;Hao Tang;Junyue Xing;Xiuqin Fan;Xiaoyu Cai;Qiu Li;Pei Han;Yuhong Luo;Zhuojun Zhang;Bin Jiang;Y. Dou;M. Gorospe;Wengong Wang
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文献类型：
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作者：
Shuai Yuan;Hao Tang;Junyue Xing;Xiuqin Fan;Xiaoyu Cai;Qiu Li;Pei Han;Yuhong Luo;Zhuojun Zhang;Bin Jiang;Y. Dou;M. Gorospe;Wengong Wang
摘要甲基化是RNA转录后修饰的一种普遍现象。然而，哺乳动物microRNA是否被甲基化尚不清楚。在这里，我们表明tRNA甲基转移酶NSun 2在体外和体内甲基化初级（pri-miR-125 b）、前体（pre-miR-125 b）和成熟microRNA 125 b（miR-125 b）。NSun 2的甲基化抑制了pri-miR-125 b2加工成pre-miR-125 b2，减少了pre-miR-125 b2切割成miR-125，并减弱了miR-125对RISC的募集，从而抑制了miR-125 b在沉默基因表达中的功能。我们的研究结果强调了miR-125 b功能通过NSun 2甲基化的影响。
ABSTRACT Methylation is a prevalent posttranscriptional modification of RNAs. However, whether mammalian microRNAs are methylated is unknown. Here, we show that the tRNA methyltransferase NSun2 methylates primary (pri-miR-125b), precursor (pre-miR-125b), and mature microRNA 125b (miR-125b) in vitro and in vivo. Methylation by NSun2 inhibits the processing of pri-miR-125b2 into pre-miR-125b2, decreases the cleavage of pre-miR-125b2 into miR-125, and attenuates the recruitment of RISC by miR-125, thereby repressing the function of miR-125b in silencing gene expression. Our results highlight the impact of miR-125b function via methylation by NSun2.