SPT5 stabilization of promoter-proximal RNA polymerase II

Yuki Aoi, Yoh hei Takahashi, Avani P. Shah, Marta Iwanaszko, Emily J. Rendleman, Nabiha H. Khan, Byoung Kyu Cho, Young Ah Goo, Sheetal Ganesan, Neil L. Kelleher, Ali Shilatifard

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Based on in vitro studies, it has been demonstrated that the DSIF complex, composed of SPT4 and SPT5, regulates the elongation stage of transcription catalyzed by RNA polymerase II (RNA Pol II). The precise cellular function of SPT5 is not clear, because conventional gene depletion strategies for SPT5 result in loss of cellular viability. Using an acute inducible protein depletion strategy to circumvent this issue, we report that SPT5 loss triggers the ubiquitination and proteasomal degradation of the core RNA Pol II subunit RPB1, a process that we show to be evolutionarily conserved from yeast to human cells. RPB1 degradation requires the E3 ligase Cullin 3, the unfoldase VCP/p97, and a novel form of CDK9 kinase complex. Our study demonstrates that SPT5 stabilizes RNA Pol II specifically at promoter-proximal regions, permitting RNA Pol II release from promoters into gene bodies and providing mechanistic insight into the cellular function of SPT5 in safeguarding accurate gene expression.

Original languageEnglish
Pages (from-to)4413-4424.e5
JournalMolecular cell
Volume81
Issue number21
DOIs
StatePublished - Nov 4 2021

Keywords

  • CDK9
  • Cullin 3
  • NELF
  • RNA polymerase II
  • SPT5
  • VCP
  • auxin-inducible degron
  • degradation
  • elongation
  • transcription

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