Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export

Nat Cell Biol. 2008 Jun;10(6):707-15. doi: 10.1038/ncb1733. Epub 2008 May 18.

Abstract

Targeting of a gene to the nuclear pore complexes (NPCs), known as gene gating, can affect its transcriptional state. However, the mechanism underlying gene gating is poorly understood. Here, we have identified SAGA-associated Sgf73 (ref. 10), the yeast orthologue of human Ataxin-7 (ref. 11), as a regulator of histone H2B ubiquitin levels, a modification linked to both transcription initiation and elongation. Sgf73 is a key component of a minimal histone-deubiquitinating complex. Activation of the H2B deubiquitinating protease, Ubp8, is cooperative and requires complex formation with the amino-terminal zinc-finger-containing domain of Sgf73 and Sgf11-Sus1. Through a separate domain, Sgf73 mediates recruitment of the TREX-2 mRNA export factors Sac3 and Thp1 to SAGA and their stable interaction with Sus1-Cdc31. This latter step is crucial to target TREX-2 to the NPC. Loss of Sgf73 from SAGA abrogates gene gating of GAL1 and causes a GAL1 mRNA export defect. Thus, Sgf73 provides a molecular scaffold to integrate the regulation of H2B ubiquitin levels, tethering of a gene to the NPC and export of mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxin-7
  • Endopeptidases / metabolism
  • Gene Expression Regulation, Fungal
  • Gene Targeting
  • Histone Acetyltransferases / metabolism
  • Histones / metabolism*
  • Humans
  • Models, Biological
  • Models, Genetic
  • Nerve Tissue Proteins / physiology*
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • RNA Transport
  • RNA, Messenger / metabolism*
  • Saccharomyces cerevisiae / metabolism*

Substances

  • ATXN7 protein, human
  • Ataxin-7
  • Histones
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Histone Acetyltransferases
  • Sgf73 protein, S cerevisiae
  • Endopeptidases
  • UBP8 protein, S cerevisiae