The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation.
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.
Gwizdek
Carole
C
Institut Jacques Monod, Unité Mixte de Recherche 7592, CNRS, Universités Paris VI and VII, 75251 Paris Cedex 05, France.
Hobeika
Maria
M
Kus
Bart
B
Ossareh-Nazari
Batool
B
Dargemont
Catherine
C
Rodriguez
Manuel S
MS
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D009687:Nuclear Proteins; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013696:Temperature; D014158:Transcription, Genetic; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; C063494:HPR1 protein, S cerevisiae; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D025821:Polyubiquitin; C501306:Ubc4 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D020930:MAP Kinase Kinase Kinases; C414538:MAP kinase kinase kinase ubc4; D046988:Proteasome Endopeptidase Complex; C469287:RSP5 protein, S cerevisiae