生物
解旋酶
RNA解旋酶A
抄写(语言学)
细胞生物学
核糖核酸
染色质
转录因子
遗传学
DNA
基因
哲学
语言学
作者
Jindong Hao,Qian-Lan Liu,Min Liu,Xing Yang,Liu-Ming Wang,Shanna Su,Wen Xu,Mengqi Zhang,Yi-Chang Zhang,Lan Zhang,Yu‐Sheng Chen,Yun‐Gui Yang,Jie Ren
标识
DOI:10.1016/j.molcel.2024.03.006
摘要
N6-methyladenosine (m6A) is a crucial RNA modification that regulates diverse biological processes in human cells, but its co-transcriptional deposition and functions remain poorly understood. Here, we identified the RNA helicase DDX21 with a previously unrecognized role in directing m6A modification on nascent RNA for co-transcriptional regulation. DDX21 interacts with METTL3 for co-recruitment to chromatin through its recognition of R-loops, which can be formed co-transcriptionally as nascent transcripts hybridize onto the template DNA strand. Moreover, DDX21's helicase activity is needed for METTL3-mediated m6A deposition onto nascent RNA following recruitment. At transcription termination regions, this nexus of actions promotes XRN2-mediated termination of RNAPII transcription. Disruption of any of these steps, including the loss of DDX21, METTL3, or their enzymatic activities, leads to defective termination that can induce DNA damage. Therefore, we propose that the R-loop-DDX21-METTL3 nexus forges the missing link for co-transcriptional modification of m6A, coordinating transcription termination and genome stability.
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