Cell Reports ( IF 7.5 ) Pub Date : 2022-04-13 , DOI: 10.1016/j.celrep.2022.110673
Shin-Ichiro Ohno 1 , Keiki Oikawa 1 , Toshiaki Tsurui 1 , Yuichirou Harada 1 , Kana Ono 1 , Mizumo Tateishi 1 , Aashiq Mirza 2 , Masakatsu Takanashi 1 , Kosuke Kanekura 1 , Kumiko Nagase 3 , Yoshihisa Shimada 3 , Yujin Kudo 3 , Norihiko Ikeda 3 , Takahiro Ochiya 4 , Xiaozhong Wang 5 , Masahiko Kuroda 1
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RNA activation (RNAa) is an uncharacterized mechanism of transcriptional activation mediated by small RNAs, such as microRNAs (miRNAs). A critical issue in RNAa research is that it is difficult to distinguish between changes in gene expression caused indirectly by post-transcriptional regulation and direct induction of gene expression by RNAa. Therefore, in this study, we seek to identify a key factor involved in RNAa, using the induction of ZMYND10 by miR-34a as a system to evaluate RNAa. We identify the positive transcription elongation factors CDK9 and DDX21, which form a complex with nuclear AGO and TNRC6A, as important transcriptional activators of RNAa. In addition, we find that inhibition of DDX21 suppresses RNAa by miR-34a and other miRNAs without inhibiting post-transcriptional regulation. Our findings reveal a strong connection between RNAa and release of paused Pol II, facilitating RNAa research by making it possible to separately analyze post-transcriptional regulation and RNAa.
中文翻译:

核 microRNA 通过 DDX21-CDK9 复合物释放暂停的 Pol II
RNA 激活 (RNAa) 是一种由小 RNA 介导的转录激活机制,如 microRNA (miRNA)。RNAa 研究中的一个关键问题是很难区分由转录后调控间接引起的基因表达变化和 RNAa 直接诱导基因表达的变化。因此,在本研究中,我们试图通过诱导ZMYND10来确定 RNAa 中的一个关键因素。通过 miR-34a 作为评估 RNAa 的系统。我们将与核 AGO 和 TNRC6A 形成复合物的正转录延伸因子 CDK9 和 DDX21 鉴定为重要的 RNAa 转录激活因子。此外,我们发现抑制 DDX21 会抑制 miR-34a 和其他 miRNA 的 RNAa,而不抑制转录后调节。我们的研究结果揭示了 RNAa 与暂停的 Pol II 释放之间的密切联系,通过使单独分析转录后调控和 RNAa 成为可能,促进了 RNAa 研究。