Pcf11 orchestrates transcription termination pathways in yeast

Pawel Grzechnik, Michal Ryszard Gdula, Nick J Proudfoot

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)
22 Downloads (Pure)

Abstract

In Saccharomyces cerevisiae, short noncoding RNA (ncRNA) generated by RNA polymerase II (Pol II) are terminated by the NRD complex consisting of Nrd1, Nab3, and Sen1. We now show that Pcf11, a component of the cleavage and polyadenylation complex (CPAC), is also generally required for NRD-dependent transcription termination through the action of its C-terminal domain (CTD)-interacting domain (CID). Pcf11 localizes downstream from Nrd1 on NRD terminators, and its recruitment depends on Nrd1. Furthermore, mutation of the Pcf11 CID results in Nrd1 retention on chromatin, delayed degradation of ncRNA, and restricted Pol II CTD Ser2 phosphorylation and Sen1-Pol II interaction. Finally, the pcf11-13 and sen1-1 mutant phenotypes are very similar, as both accumulate RNA:DNA hybrids and display Pol II pausing downstream from NRD terminators. We predict a mechanism by which the exchange of Nrd1 and Pcf11 on chromatin facilitates Pol II pausing and CTD Ser2-P phosphorylation. This in turn promotes Sen1 activity that is required for NRD-dependent transcription termination in vivo.

Original languageEnglish
Pages (from-to)849-861
Number of pages13
JournalGenes & Development
Volume29
Issue number8
DOIs
Publication statusPublished - 15 Apr 2015

Keywords

  • DNA Helicases
  • Protein Structure, Tertiary
  • RNA Helicases
  • RNA, Untranslated
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Termination, Genetic
  • mRNA Cleavage and Polyadenylation Factors
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • NRD complex
  • CTD phosphorylation
  • cleavage and polyadenylation complex
  • noncoding RNA

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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