Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export.
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.
Köhler
Alwin
A
Biochemie-Zentrum der Universität Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.
Schneider
Maren
M
Cabal
Ghislain G
GG
Nehrbass
Ulf
U
Hurt
Ed
E
D000067719:Ataxin-7; D010450:Endopeptidases / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D018390:Gene Targeting; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D034443:RNA Transport; D012333:RNA, Messenger / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D006657:Histones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D051548:Histone Acetyltransferases; C515833:Sgf73 protein, S cerevisiae; D010450:Endopeptidases; C503322:UBP8 protein, S cerevisiae