Nuclear microRNAs release paused Pol II via the DDX21-CDK9 complex

• Main Authors: Harada, Y. (Author), Ikeda, N. (Author), Kanekura, K. (Author), Kudo, Y. (Author), Kuroda, M. (Author), Mirza, A. (Author), Nagase, K. (Author), Ochiya, T. (Author), Ohno, S.-I (Author), Oikawa, K. (Author), Ono, K. (Author), Shimada, Y. (Author), Takanashi, M. (Author), Tateishi, M. (Author), Tsurui, T. (Author), Wang, X. (Author)
• Format: Article
• Language: English
• Published: Elsevier B.V. 2022
• Subjects: CDK9; CP: Molecular biology; DDX21; divergent transcription; microRNA; miR-34; promoter-associated noncoding RNA; RNA activation; small activating RNA; ZMYND10
• Online Access: View Fulltext in Publisher

 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. © 2022 The Author(s)