N6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription
N6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription
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DOI：
10.1126/science.aay6018
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发表时间：
2020-01-31
期刊：
影响因子：
56.9
通讯作者：
Hei, Chuan
中科院分区：
文献类型：
--
作者：
Liu, Jun;Do, Xiaoyang;Hei, Chuan
N-6-甲基读腺苷（M（6）a）在各种生物学过程中调节了信使RNA（mRNA）的稳定性和翻译。在这项工作中，我们表明M（6）在小鼠胚胎干细胞中的作者METTL3或核读取器YTHDC1的敲除可增加染色质的可及性，并以M（6）A依赖性方式激活转录。我们发现Mettl3沉积M（6）对染色体相关的调节RNA（CARRNA）的修改，包括启动子相关的RNA，增强子RNA和重复RNA。 YTHDC1通过靶向介导的核介导的核降解，促进了这些M（6）A修饰的RNA的子集的衰减，尤其是长期散布元素-1家族的元素。通过Mettl3耗竭或位点特异性M（6）降低M（6）A甲基化甲基化的甲基化脱甲基的脱甲基化提高了Carrnas的水平并促进开放的染色质状态和下游转录。总体而言，我们的结果表明，M（6）A上的ANA上可以全球调整染色质状态和转录。
N-6-methyladenosine (m(6)A) regulates stability and translation of messenger RNA (mRNA) in various biological processes. In this work, we show that knockout of the m(6)A writer Mettl3 or the nuclear reader Ythdc1 in mouse embryonic stem cells increases chromatin accessibility and activates transcription in an m(6)A-dependent manner. We found that METTL3 deposits m(6)A modifications on chromosome-associated regulatory RNAs (carRNAs), including promoter-associated RNAs, enhancer RNAs, and repeat RNAs. YTHDC1 facilitates the decay of a subset of these m(6)A-modified RNAs, especially elements of the long interspersed element-1 family, through the nuclear exosome targeting-mediated nuclear degradation. Reducing m(6)A methylation by METTL3 depletion or site-specific m(6)A demethylation of selected carRNAs elevates the levels of carRNAs and promotes open chromatin state and downstream transcription. Collectively, our results reveal that m(6)A on carRNAs can globally tune chromatin state and transcription.