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, Claus D. Kuhn

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number2429
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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