PMID:15713680

Citation	Gwizdek, C, Hobeika, M, Kus, B, Ossareh-Nazari, B, Dargemont, C and Rodriguez, MS (2005) The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation. J. Biol. Chem. 280:13401-5
Abstract	Ubiquitin conjugation and in particular two distinct HECT ubiquitin ligases, Rsp5p and Tom1p, have been shown to participate in the regulation of mRNA export in Saccharomyces cerevisiae. The identification of the ubiquitin ligase substrates represents a major challenge in understanding how this modification may modulate mRNA export. Here, we identified Hpr1p, a member of the THO/TREX (transcription/export) complex that couples mRNA transcription to nuclear export as a target of the ubiquitin-proteasome pathway. Hpr1p degradation is enhanced at high temperature and appears linked to on-going RNA-polymeraseII-mediated transcription. Interestingly, the stability of the other THO complex components is not affected under these conditions indicating that Hpr1p turnover could control the formation of the THO/TREX complex and consequently mRNA export. Using in vivo and in vitro approaches we demonstrate that Rsp5p is responsible for the ubiquitylation of Hpr1p that also involves the ubiquitin-conjugating enzyme Ubc4p. Thus, Hpr1p represents the first nuclear export factor regulated by ubiquitylation, strongly suggesting that this post-translational modification participates in the coordination of transcription and mRNA export processes.
Links	PubMed Online version:10.1074/jbc.C500040200
Keywords	Active Transport, Cell Nucleus/physiology; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Endosomal Sorting Complexes Required for Transport; MAP Kinase Kinase Kinases/metabolism; Nuclear Proteins; Polyubiquitin/metabolism; Proteasome Endopeptidase Complex/metabolism; Protein Processing, Post-Translational; RNA, Messenger/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Temperature; Transcription, Genetic; Ubiquitin-Conjugating Enzymes/genetics; Ubiquitin-Conjugating Enzymes/metabolism; Ubiquitin-Protein Ligase Complexes/genetics; Ubiquitin-Protein Ligase Complexes/metabolism
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