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.
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Gene/Complex | Qualifier | Gene Ontology Term | Annotation Extension | Evidence | Source | Assigned On |
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RSP5 | involved in | proteasome-mediated ubiquitin-dependent protein catabolic process | IPI with HPR1 | SGD | 2013-08-07 | |
RSP5 | involved in | regulation of mRNA export from nucleus | IPI with HPR1 | SGD | 2013-08-07 |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Interactor | Interactor | Assay | Annotation | Action | Modification | |
---|---|---|---|---|---|---|
RSP5 | HPR1 | Reconstituted Complex | manually curated | Bait-Hit | No Modification | |
RSP5 | BUL1 | Reconstituted Complex | manually curated | Bait-Hit | No Modification | |
RSP5 | HPR1 | Biochemical Activity | manually curated | Bait-Hit | ubiquitinylated lysine | |
RSP5 | RPO21 | Biochemical Activity | manually curated | Bait-Hit | ubiquitinylated lysine | |
E2:Ubc4 | UBC4 | RSP5 | Reconstituted Complex | manually curated | Hit-Bait | No Modification |