Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF

Vladyslava Gorbovytska, Seung-Kyoon Kim, Filiz Kuybu, Michael Götze, Dahun Um, Keunsoo Kang, Andreas Pittroff, Theresia Brennecke, Lisa-Marie Schneider, Alexander Leitner, Tae-Kyung Kim () and Claus-D. Kuhn ()
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Vladyslava Gorbovytska: University of Bayreuth
Seung-Kyoon Kim: Pohang University of Science and Technology (POSTECH)
Filiz Kuybu: University of Bayreuth
Michael Götze: Institute of Molecular Systems Biology, ETH Zurich
Dahun Um: Pohang University of Science and Technology (POSTECH)
Keunsoo Kang: Dankook University
Andreas Pittroff: University of Bayreuth
Theresia Brennecke: University of Bayreuth
Lisa-Marie Schneider: University of Bayreuth
Alexander Leitner: Institute of Molecular Systems Biology, ETH Zurich
Tae-Kyung Kim: Pohang University of Science and Technology (POSTECH)
Claus-D. Kuhn: University of Bayreuth

Nature Communications, 2022, vol. 13, issue 1, 1-22

Abstract: Abstract Enhancer RNAs (eRNAs) are long non-coding RNAs that originate from enhancers. Although eRNA transcription is a canonical feature of activated enhancers, the molecular features required for eRNA function and the mechanism of how eRNAs impinge on target gene transcription have not been established. Thus, using eRNA-dependent RNA polymerase II (Pol II) pause release as a model, we here investigate the requirement of sequence, structure and length of eRNAs for their ability to stimulate Pol II pause release by detaching NELF from paused Pol II. We find eRNAs not to exert their function through common structural or sequence motifs. Instead, eRNAs that exhibit a length >200 nucleotides and that contain unpaired guanosines make multiple, allosteric contacts with NELF subunits -A and -E to trigger efficient NELF release. By revealing the molecular determinants of eRNA function, our study establishes eRNAs as an important player in Pol II pause release, and it provides new insight into the regulation of metazoan transcription.

Date: 2022
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DOI: 10.1038/s41467-022-29934-w

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