m6A RNA methylation regulates promoter-proximal pausing of RNA polymerase II
m6A RNA methylation regulates promoter-proximal pausing of RNA polymerase II
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DOI：
10.1016/j.molcel.2021.06.023
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发表时间：
2021-08-19
期刊：
影响因子：
16
通讯作者：
Junion, Guillaume
中科院分区：
文献类型：
--
作者：
Akhtar, Junaid;Renaud, Yoan;Junion, Guillaume
RNA聚合酶II（RNAP II）暂停对于精确控制基因表达至关重要，并且对后生动物的发育至关重要。在此，我们表明m(6)A RNA修饰调控果蝇细胞中启动子近端的RNAP II暂停。m(6)A甲基转移酶复合物（MTC）和核内阅读蛋白Ythdc1被招募到基因启动子上。去除m(6)A MTC会导致RNAP II暂停释放减少以及基因体上Ser2P的占位减少，并影响新生RNA转录。将Mettl3连接到异源基因启动子上足以增加RNAP II暂停释放，这种效应依赖于其m(6)A催化结构域。总之，我们的数据揭示了RNAP II暂停与m(6)A RNA修饰之间的重要联系，从而为m(6)A介导的基因调控增添了新的层面。
RNA polymerase II (RNAP II) pausing is essential to precisely control gene expression and is critical for development of metazoans. Here, we show that the m(6)A RNA modification regulates promoter-proximal RNAP II pausing in Drosophila cells. The m(6)A methyltransferase complex (MTC) and the nuclear reader Ythdc1 are recruited to gene promoters. Depleting the m(6)A MTC leads to a decrease in RNAP II pause release and in Ser2P occupancy on the gene body and affects nascent RNA transcription. Tethering Mettl3 to a heterologous gene promoter is sufficient to increase RNAP II pause release, an effect that relies on its m(6)A catalytic domain. Collectively, our data reveal an important link between RNAP II pausing and the m(6)A RNA modification, thus adding another layer to m(6)A-mediated gene regulation.