A new layer of transcriptional control N6-methyladenosine (m6A) is the most abundant messenger RNA modification in almost all eukaryotes. Liu et al. now show that m6A is also cotranscriptionally added onto various chromosome-associated regulatory RNAs (carRNAs) in mammalian cells. Disruption of m6A modification of these RNAs increases their abundance and promotes gene transcription by increasing the chromatin accessibility. Thus, m6A serves as a switch to regulate carRNA levels by tuning nearby chromatin state and downstream transcription. Science, this issue p. 580 Chromosome-associated regulatory RNAs modified by N6-methyladenosine regulate chromatin and transcription. N6-methyladenosine (m6A) regulates stability and translation of messenger RNA (mRNA) in various biological processes. In this work, we show that knockout of the m6A writer Mettl3 or the 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 repeat RNAs. YTHDC1 facilitates the decay of a subset of these m6A-modified RNAs, especially elements of the long interspersed element-1 family, through the nuclear exosome targeting–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 reveal that m6A on carRNAs can globally tune chromatin state and transcription.

中文翻译：

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染色体相关调节RNA的N6-甲基腺苷调节染色质状态和转录

新的转录控制层 N6-甲基腺苷 (m6A) 是几乎所有真核生物中最丰富的信使 RNA 修饰。刘等人。现在表明 m6A 也被共转录添加到哺乳动物细胞中的各种染色体相关调节 RNA (carRNAs) 上。破坏这些 RNA 的 m6A 修饰会增加它们的丰度并通过增加染色质的可及性来促进基因转录。因此，m6A 作为一个开关，通过调节附近的染色质状态和下游转录来调节 carRNA 水平。科学，这个问题 p。由 N6-甲基腺苷修饰的 580 个与染色体相关的调节 RNA 调节染色质和转录。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。在这项工作中，我们表明在小鼠胚胎干细胞中敲除 m6A 写入器 Mettl3 或核读取器 Ythdc1 会增加染色质的可及性并以 m6A 依赖性方式激活转录。我们发现 METTL3 将 m6A 修饰沉积在染色体相关的调控 RNA (carRNA) 上，包括启动子相关的 RNA、增强子 RNA 和重复 RNA。YTHDC1 通过核外泌体靶向介导的核降解促进了这些 m6A 修饰的 RNA 子集的衰变，尤其是长散布的 element-1 家族的元素。通过 METTL3 耗竭或选定 carRNA 的位点特异性 m6A 去甲基化减少 m6A 甲基化，可提高 carRNA 的水平并促进开放染色质状态和下游转录。总的来说，