Genome-wide Analysis of RNA Polymerase II Termination at Protein-Coding Genes

Mol Cell. 2017 Apr 6;66(1):38-49.e6. doi: 10.1016/j.molcel.2017.02.009. Epub 2017 Mar 16.

Abstract

At the end of protein-coding genes, RNA polymerase (Pol) II undergoes a concerted transition that involves 3'-processing of the pre-mRNA and transcription termination. Here, we present a genome-wide analysis of the 3'-transition in budding yeast. We find that the 3'-transition globally requires the Pol II elongation factor Spt5 and factors involved in the recognition of the polyadenylation (pA) site and in endonucleolytic RNA cleavage. Pol II release from DNA occurs in a narrow termination window downstream of the pA site and requires the "torpedo" exonuclease Rat1 (XRN2 in human). The Rat1-interacting factor Rai1 contributes to RNA degradation downstream of the pA site. Defects in the 3'-transition can result in increased transcription at downstream genes.

Keywords: RNA polymerase II; Torpedo nuclease; poly-adenylation; pre-mRNA 3′-processing; transcription termination.

MeSH terms

  • Binding Sites
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism*
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism
  • Models, Genetic
  • Protein Binding
  • RNA 3' End Processing*
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • RNA Precursors / biosynthesis*
  • RNA Precursors / genetics
  • RNA, Fungal / biosynthesis*
  • RNA, Fungal / genetics
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA, Fungal
  • PCF11 protein, S cerevisiae
  • RNA Precursors
  • RNA, Fungal
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Transcriptional Elongation Factors
  • YSH1 protein, S cerevisiae
  • mRNA Cleavage and Polyadenylation Factors
  • SPT5 transcriptional elongation factor
  • RAT1 protein, S cerevisiae
  • RNA Polymerase II
  • Exoribonucleases