The Nrd1-like protein Seb1 coordinates cotranscriptional 3′ end processing and polyadenylation site selection

  1. François Bachand1
  1. 1RNA Group, Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Quebec J1E 4K8, Canada;
  2. 2MRC Clinical Sciences Centre (CSC), London W12 0NN, United Kingdom;
  3. 3Institute of Clinical Sciences (ICS), Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom;
  4. 4Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey 07103, USA;
  5. 5Rutgers Cancer Institute of New Jersey, Newark, New Jersey 08903, USA;
  6. 6Centre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh EH9 3BF, United Kingdom;
  7. 7Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, United Kingdom;
  8. 8Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, United Kingdom
  1. Corresponding author: f.bachand{at}usherbrooke.ca
  1. 9 These authors contributed equally to this work.

Abstract

Termination of RNA polymerase II (RNAPII) transcription is associated with RNA 3′ end formation. For coding genes, termination is initiated by the cleavage/polyadenylation machinery. In contrast, a majority of noncoding transcription events in Saccharomyces cerevisiae does not rely on RNA cleavage for termination but instead terminates via a pathway that requires the Nrd1–Nab3–Sen1 (NNS) complex. Here we show that the Schizosaccharomyces pombe ortholog of Nrd1, Seb1, does not function in NNS-like termination but promotes polyadenylation site selection of coding and noncoding genes. We found that Seb1 associates with 3′ end processing factors, is enriched at the 3′ end of genes, and binds RNA motifs downstream from cleavage sites. Importantly, a deficiency in Seb1 resulted in widespread changes in 3′ untranslated region (UTR) length as a consequence of increased alternative polyadenylation. Given that Seb1 levels affected the recruitment of conserved 3′ end processing factors, our findings indicate that the conserved RNA-binding protein Seb1 cotranscriptionally controls alternative polyadenylation.

Keywords

Footnotes

  • Received February 29, 2016.
  • Accepted June 10, 2016.

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