Journal
CELL REPORTS
Volume 39, Issue 2, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.110673
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Funding
- JSPS KAKENHI [15K08410, 17K15671, 18K07048, 17H04067, 21H02706, 21K06953]
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) [S1511011]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [21K06953, 17K15671, 15K08410, 21H02706, 17H04067, 18K07048] Funding Source: KAKEN
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CDK9 and DDX21 are identified as important transcriptional activators of RNAa, forming a complex with nuclear AGO and TNRC6A. Inhibition of DDX21 can suppress RNAa by miR-34a and other miRNAs without affecting post-transcriptional regulation, facilitating the separate analysis of RNAa and post-transcriptional regulation.
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.
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