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Shape of promoter antisense RNAs regulates ligand-induced transcription activation

Author

Listed:
  • Fan Yang

    (University of California, San Diego)

  • Bogdan Tanasa

    (Stanford University School of Medicine)

  • Rudi Micheletti

    (University of California, San Diego)

  • Kenneth A. Ohgi

    (University of California, San Diego)

  • Aneel K. Aggarwal

    (Icahn School of Medicine at Mount Sinai)

  • Michael G. Rosenfeld

    (University of California, San Diego)

Abstract

The size of the transcriptional program of long non-coding RNAs in the mammalian genome has engendered discussions about their biological roles1, particularly the promoter antisense (PAS) transcripts2,3. Here we report the development of an assay—referred to as chromatin isolation by RNA–Cas13a complex—to quantitatively detect the distribution of RNA in the genome. The assay revealed that PAS RNAs serve as a key gatekeeper of a broad transcriptional pause release program, based on decommissioning the 7SK small nuclear RNA-dependent inhibitory P-TEFb complex. Induction of PAS RNAs by liganded ERα led to a significant loss of H3K9me3 and the release of basally recruited HP1α and KAP1 on activated target gene promoters. This release was due to PAS RNA-dependent recruitment of H3K9me3 demethylases, which required interactions with a compact stem-loop structure in the PAS RNAs, an apparent feature of similarly regulated PAS RNAs. Activation of the ERα-bound MegaTrans enhancer, which is essential for robust pause release, required the recruitment of phosphorylated KAP1, with its transfer to the cognate promoters permitting 17β-oestradiol-induced pause release and activation of the target gene. This study reveals a mechanism, based on RNA structure, that mediates the function of PAS RNAs in gene regulation.

Suggested Citation

  • Fan Yang & Bogdan Tanasa & Rudi Micheletti & Kenneth A. Ohgi & Aneel K. Aggarwal & Michael G. Rosenfeld, 2021. "Shape of promoter antisense RNAs regulates ligand-induced transcription activation," Nature, Nature, vol. 595(7867), pages 444-449, July.
    • Handle: RePEc:nat:nature:v:595:y:2021:i:7867:d:10.1038_s41586-021-03589-x
    DOI: 10.1038/s41586-021-03589-x
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    Cited by:

    1. Xavier Contreras & David Depierre & Charbel Akkawi & Marina Srbic & Marion Helsmoortel & Maguelone Nogaret & Matthieu LeHars & Kader Salifou & Alexandre Heurteau & Olivier Cuvier & Rosemary Kiernan, 2023. "PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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