Publications (2)10.26 Total impact
Article: Sem1: a versatile "molecular glue"?[show abstract] [hide abstract]
ABSTRACT: The evolutionary conserved protein Sem1/Dss1 is a bona fide subunit of the regulatory particle (RP) of the proteasome and in mammalian cells stabilizes the tumor suppressor protein BRCA2. A recent study from our laboratory has revealed an unexpected non- proteasomal role of Sem1 in mRNA export. We found that Sem1, independent of the RP, is a functional component of the nuclear pore associated TREX-2 complex that is directly involved in the dynamic relocalization of a subset of DNA loci to the nuclear periphery. Like other components of TREX-2, Sem1 is required for proper nuclear export of mRNAs, transcription elongation and preventing transcription-associated genomic instability. Strikingly, Sem1 associates with a third multi-subunit protein complex namely the COP9 signalosome, which is involved in de-neddylation. We propose that Sem1 is a versatile protein that regulates the functional integrity of multiple protein complexes involved in diverse biological pathways.Nucleus (Austin, Texas) 01/2010; 1(1):12-7.
Article: Sem1 is a functional component of the nuclear pore complex-associated messenger RNA export machinery.[show abstract] [hide abstract]
ABSTRACT: The evolutionarily conserved protein Sem1/Dss1 is a subunit of the regulatory particle (RP) of the proteasome, and, in mammalian cells, binds the tumor suppressor protein BRCA2. Here, we describe a new function for yeast Sem1. We show that sem1 mutants are impaired in messenger RNA (mRNA) export and transcription elongation, and induce strong transcription-associated hyper-recombination phenotypes. Importantly, Sem1, independent of the RP, is functionally linked to the mRNA export pathway. Biochemical analyses revealed that, in addition to the RP, Sem1 coenriches with components of two other multisubunit complexes: the nuclear pore complex (NPC)-associated TREX-2 complex that is required for transcription-coupled mRNA export, and the COP9 signalosome, which is involved in deneddylation. Notably, targeting of Thp1, a TREX-2 component, to the NPC is perturbed in a sem1 mutant. These findings reveal an unexpected nonproteasomal function of Sem1 in mRNA export and in prevention of transcription-associated genome instability. Thus, Sem1 is a versatile protein that might stabilize multiple protein complexes involved in diverse pathways.The Journal of Cell Biology 04/2009; 184(6):833-46. · 10.26 Impact Factor