RNA Polymerase II CTD Tyrosine 1 Is Required for Efficient Termination by the Nrd1-Nab3-Sen1 Pathway

Mol Cell. 2019 Feb 21;73(4):655-669.e7. doi: 10.1016/j.molcel.2018.12.002. Epub 2019 Jan 10.


In Saccharomyces cerevisiae, transcription termination at protein-coding genes is coupled to the cleavage of the nascent transcript, whereas most non-coding RNA transcription relies on a cleavage-independent termination pathway involving Nrd1, Nab3, and Sen1 (NNS). Termination involves RNA polymerase II CTD phosphorylation, but a systematic analysis of the contribution of individual residues would improve our understanding of the role of the CTD in this process. Here we investigated the effect of mutating phosphorylation sites in the CTD on termination. We observed widespread termination defects at protein-coding genes in mutants for Ser2 or Thr4 but rare defects in Tyr1 mutants for this genes class. Instead, mutating Tyr1 led to widespread termination defects at non-coding genes terminating via NNS. Finally, we showed that Tyr1 is important for pausing in the 5' end of genes and that slowing down transcription suppresses termination defects. Our work highlights the importance of Tyr1-mediated pausing in NNS-dependent termination.

Keywords: CTD; Nab3; Nrd1; Pcf11; Pol II; Rtt103; Sen1; pausing; transcription termination; tyrosine 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Gene Expression Regulation, Fungal
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Time Factors
  • Transcription Termination, Genetic*
  • Tyrosine


  • NAB3 protein, S cerevisiae
  • NRD1 protein, S cerevisiae
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • Tyrosine
  • RNA Polymerase II
  • SEN1 protein, S cerevisiae
  • DNA Helicases
  • RNA Helicases