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

Shin ichiro Ohno, Keiki Oikawa, Toshiaki Tsurui, Yuichirou Harada, Kana Ono, Mizumo Tateishi, Aashiq Mirza, Masakatsu Takanashi, Kosuke Kanekura, Kumiko Nagase, Yoshihisa Shimada, Yujin Kudo, Norihiko Ikeda, Takahiro Ochiya, Xiaozhong Wang, Masahiko Kuroda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish (US)
Article number110673
JournalCell reports
Issue number2
StatePublished - Apr 12 2022


  • CDK9
  • CP: Molecular biology
  • DDX21
  • RNA activation
  • ZMYND10
  • divergent transcription
  • miR-34
  • microRNA
  • promoter-associated noncoding RNA
  • small activating RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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