Institute of Developmental Biology and Neurobiology, University of Mainz, 55128 Mainz, Germany.
Université Clermont Auvergne, CNRS UMR6293, Inserm U1103, GReD institute, 63000 Clermont-Ferrand, France.
Mol Cell. 2021 Aug 19;81(16):3356-3367.e6. doi: 10.1016/j.molcel.2021.06.023. Epub 2021 Jul 22.
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 mA RNA modification regulates promoter-proximal RNAP II pausing in Drosophila cells. The mA methyltransferase complex (MTC) and the nuclear reader Ythdc1 are recruited to gene promoters. Depleting the mA 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 mA catalytic domain. Collectively, our data reveal an important link between RNAP II pausing and the mA RNA modification, thus adding another layer to mA-mediated gene regulation.
RNA 聚合酶 II（RNAP II）暂停对于精确控制基因表达至关重要，对后生动物的发育也很关键。在这里，我们表明 mA RNA 修饰调控了果蝇细胞中启动子近端的 RNAP II 暂停。mA 甲基转移酶复合物（MTC）和核读蛋白 Ythdc1 被招募到基因启动子上。耗尽 mA MTC 会导致 RNAP II 暂停释放减少，以及基因体上 Ser2P 占有率降低，并影响新生 RNA 转录。将 Mettl3 固定在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 mA 催化结构域。总的来说，我们的数据揭示了 RNAP II 暂停和 mA RNA 修饰之间的重要联系，从而为 mA 介导的基因调控增加了另一个层面。
