The Chromatin Remodeler ISW1 Is a Quality Control Factor that Surveys Nuclear mRNP Biogenesis

Cell. 2016 Nov 17;167(5):1201-1214.e15. doi: 10.1016/j.cell.2016.10.048.

Abstract

Chromatin dynamics play an essential role in regulating DNA transaction processes, but it is unclear whether transcription-associated chromatin modifications control the mRNA ribonucleoparticles (mRNPs) pipeline from synthesis to nuclear exit. Here, we identify the yeast ISW1 chromatin remodeling complex as an unanticipated mRNP nuclear export surveillance factor that retains export-incompetent transcripts near their transcription site. This tethering activity of ISW1 requires chromatin binding and is independent of nucleosome sliding activity or changes in RNA polymerase II processivity. Combination of in vivo UV-crosslinking and genome-wide RNA immunoprecipitation assays show that Isw1 and its cofactors interact directly with premature mRNPs. Our results highlight that the concerted action of Isw1 and the nuclear exosome ensures accurate surveillance mechanism that proofreads the efficiency of mRNA biogenesis.

Keywords: ISWI; Isw1; Npl3; chromatin remodeler; mRNA export; mRNP biogenesis; mRNP quality control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Chromatin Assembly and Disassembly
  • DNA-Binding Proteins / metabolism*
  • Exosome Multienzyme Ribonuclease Complex / metabolism
  • Exosomes / metabolism
  • Multiprotein Complexes / metabolism
  • RNA Polymerase II / metabolism
  • Ribonucleoproteins / metabolism*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Ribonucleoproteins
  • Saccharomyces cerevisiae Proteins
  • messenger ribonucleoprotein
  • RNA Polymerase II
  • Exosome Multienzyme Ribonuclease Complex
  • RRP6 protein, S cerevisiae
  • Adenosine Triphosphatases
  • ISW1 protein, S cerevisiae