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RNA N6甲基腺苷修饰调控染色质状态和转录
作者:小柯机器人 发布时间:2020/1/20 10:54:07

美国芝加哥大学何川、中国科学院北京基因组研究所韩大力、同济大学高亚威等研究人员合作发现,染色体相关调节性RNA的N6-甲基腺苷修饰调节染色质状态和转录。相关论文于2020年1月16日在线发表于国际学术期刊《科学》。

研究人员表示,N6-甲基腺苷(m6A)在各种生物过程中调节信使RNA(mRNA)的稳定性和翻译。

研究人员发现,在小鼠胚胎干细胞中敲除m6A修饰蛋白Mettl3或核内阅读蛋白Ythdc1会增加染色质的可及性,并以m6A依赖性方式激活转录。研究人员发现METTL3在染色体相关的调控RNA(carRNA)上积累了m6A修饰,包括启动子相关的RNA、增强子RNA和重复RNA。YTHDC1通过NEXT介导的核降解促进这些m6A修饰的RNA类群(尤其是LINE1元件)的降解。通过METTL3敲低或所选carRNA的位点特异性m6A去甲基减少m6A甲基化,可提高carRNA的水平,并促进开放的染色质状态和下游转录。总的来说,这些结果表明,carRNA上的m6A可以全局性调节染色质状态和转录。

附:英文原文

Title: N6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription

Author: Jun Liu, Xiaoyang Dou, Chuanyuan Chen, Chuan Chen, Chang Liu, Meng Michelle Xu, Siqi Zhao, Bin Shen, Yawei Gao, Dali Han, Chuan He

Issue&Volume: 2020/01/16

Abstract: N6-methyladenosine (m6A) regulates stability and translation of messenger RNA (mRNA) in various biological processes. Here, we showed that knockout of the m6A writer Mettl3 or a nuclear reader Ythdc1 in mouse embryonic stem cells increases chromatin accessibility and activates transcription in an m6A-dependent manner. We found that METTL3 deposits m6A modifications on chromosome-associated regulatory RNAs (carRNAs), including promoter-associated RNAs, enhancer RNAs and repeats RNAs. YTHDC1 facilitates decay of a subset of these m6A-modified RNAs, especially LINE1 elements, through the NEXT-mediated nuclear degradation. Reducing m6A methylation by METTL3 depletion or site-specific m6A demethylation of selected carRNAs elevates the levels of carRNAs and promotes open chromatin state and downstream transcription. Collectively, our results revealed that m6A on carRNAs can globally tune chromatin state and transcription.

DOI: 10.1126/science.aay6018

Source: https://science.sciencemag.org/content/early/2020/01/15/science.aay6018

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037