PT  - JOURNAL ARTICLE
AU  - Vladyslava Gorbovytska
AU  - Seung-Kyoon Kim
AU  - Filiz Kuybu
AU  - Michael Götze
AU  - Dahun Um
AU  - Keunsoo Kang
AU  - Andreas Pittroff
AU  - Lisa-Marie Schneider
AU  - Alexander Leitner
AU  - Tae-Kyung Kim
AU  - Claus-D. Kuhn
TI  - Enhancer RNAs stimulate Pol II pause release by harnessing multivalent interactions to NELF
AID  - 10.1101/2021.04.25.441328
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.25.441328
4099  - http://biorxiv.org/content/early/2021/04/26/2021.04.25.441328.1.short
4100  - http://biorxiv.org/content/early/2021/04/26/2021.04.25.441328.1.full
AB  - 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 examined 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 found eRNA not to exert their function through common structural or sequence motifs. Instead, efficient NELF release requires a single eRNA molecule that must contain unpaired guanosines to make multiple, allosteric contacts with several NELF subunits. By revealing the molecular determinants for eRNA function, our study mechanistically links eRNAs to Pol II pause release and provides new insight into the regulation of metazoan transcription.Competing Interest StatementThe authors have declared no competing interest.