NELF Regulates a Promoter-Proximal Step Distinct from RNA Pol II Pause-Release

Yuki Aoi, Edwin R. Smith, Avani P. Shah, Emily J. Rendleman, Stacy A. Marshall, Ashley R. Woodfin, Fei X. Chen, Ramin Shiekhattar, Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

RNA polymerase II (RNA Pol II) is generally paused at promoter-proximal regions in most metazoans, and based on in vitro studies, this function has been attributed to the negative elongation factor (NELF). Here, we show that upon rapid depletion of NELF, RNA Pol II fails to be released into gene bodies, stopping instead around the +1 nucleosomal dyad-associated region. The transition to the 2nd pause region is independent of positive transcription elongation factor P-TEFb. During the heat shock response, RNA Pol II is rapidly released from pausing at heat shock-induced genes, while most genes are paused and transcriptionally downregulated. Both of these aspects of the heat shock response remain intact upon NELF loss. We find that NELF depletion results in global loss of cap-binding complex from chromatin without global reduction of nascent transcript 5′ cap stability. Thus, our studies implicate NELF functioning in early elongation complexes distinct from RNA Pol II pause-release.

Original languageEnglish (US)
Pages (from-to)261-274.e5
JournalMolecular cell
Volume78
Issue number2
DOIs
StatePublished - Apr 16 2020

Keywords

  • cap-binding complex
  • m7G cap
  • mRNA capping
  • NELF
  • PRO-cap
  • PRO-seq
  • promoter-proximal pausing
  • RNA Polymerase II
  • super elongation complex
  • transcription elongation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Aoi, Y., Smith, E. R., Shah, A. P., Rendleman, E. J., Marshall, S. A., Woodfin, A. R., Chen, F. X., Shiekhattar, R., & Shilatifard, A. (2020). NELF Regulates a Promoter-Proximal Step Distinct from RNA Pol II Pause-Release. Molecular cell, 78(2), 261-274.e5. https://doi.org/10.1016/j.molcel.2020.02.014