N4-acetylcytidine modifies primary microRNAs for processing in cancer cells.
N4-acetylcytidine modifies primary microRNAs for processing in cancer cells.
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DOI：
10.1007/s00018-023-05107-w
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发表时间：
2024-02-03
影响因子：
8
通讯作者：
Yu, Jianxiu
中科院分区：
文献类型：
--
作者：
Zhang, Hailong;Lu, Runhui;Huang, Jiayi;Li, Lian;Cao, Yingting;Huang, Caihu;Chen, Ran;Wang, Yanli;Huang, Jian;Zhao, Xian;Yu, Jianxiu
N4乙酰胞苷（ac 4C）修饰主要发生在tRNA、rRNA和mRNA上，在遗传信息的表达中起重要作用。然而，microRNA是否经历了ac 4C修饰及其潜在的生理和病理功能仍不清楚。在这项研究中，我们确定了NAT 10/THUMPD 1乙酰化具有ac 4C修饰的初级microRNA（pri-miRNAs）。NAT 10的敲低分别抑制和增强成熟miRNA和pri-miRNA的表达水平。分子机制研究发现，pri-miRNA ac 4C通过增强pri-miRNA与DGCR 8的相互作用，促进pri-miRNA加工成前体miRNA（pre-miRNA），从而增加成熟miRNA的生物合成。NAT 10的敲低通过调节癌症中miRNA的产生来减弱肺癌细胞的致癌特性。此外，NAT 10在多种临床癌症中高表达，并且与不良预后负相关。因此，我们的研究结果表明，NAT 10通过调节pri-miRNA ac 4C来影响miRNA的产生，在癌症的发生和发展中起着至关重要的作用，这将为癌症提供有吸引力的治疗策略。在线版本包含补充材料，可通过10.1007/s 00018 -023-05107-w获得。
N4 acetylcytidine (ac4C) modification mainly occurs on tRNA, rRNA, and mRNA, playing an important role in the expression of genetic information. However, it is still unclear whether microRNAs have undergone ac4C modification and their potential physiological and pathological functions. In this study, we identified that NAT10/THUMPD1 acetylates primary microRNAs (pri-miRNAs) with ac4C modification. Knockdown of NAT10 suppresses and augments the expression levels of mature miRNAs and pri-miRNAs, respectively. Molecular mechanism studies found that pri-miRNA ac4C promotes the processing of pri-miRNA into precursor miRNA (pre-miRNA) by enhancing the interaction of pri-miRNA and DGCR8, thereby increasing the biogenesis of mature miRNA. Knockdown of NAT10 attenuates the oncogenic characters of lung cancer cells by regulating miRNA production in cancers. Moreover, NAT10 is highly expressed in various clinical cancers and negatively correlated with poor prognosis. Thus, our results reveal that NAT10 plays a crucial role in cancer initiation and progression by modulating pri-miRNA ac4C to affect miRNA production, which would provide an attractive therapeutic strategy for cancers. The online version contains supplementary material available at 10.1007/s00018-023-05107-w.
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影响因子：
12.3
作者：
Wang S;Xie H;Mao F;Wang H;Wang S;Chen Z;Zhang Y;Xu Z;Xing J;Cui Z;Gao X;Jin H;Hua J;Xiong B;Wu Y
通讯作者：
Wu Y
缺氧通过诱导癌细胞中 AGO2 的 Met1 相关线性泛素化来调节整体 mRNA 稳态
影响因子：
16.6
作者：
Zhang H;Zhao X;Guo Y;Chen R;He J;Li L;Qiang Z;Yang Q;Liu X;Huang C;Lu R;Fang J;Cao Y;Huang J;Wang Y;Huang J;Chen GQ;Cheng J;Yu J
通讯作者：
Yu J
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
DOI：
10.1126/science.aad8711
发表时间：
2016-06-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert WV;Bell TA;Schaening C
通讯作者：
Schaening C
影响因子：
12.3
作者：
Tomaselli S;Galeano F;Alon S;Raho S;Galardi S;Polito VA;Presutti C;Vincenti S;Eisenberg E;Locatelli F;Gallo A
通讯作者：
Gallo A