Semi is a functional component of the nuclear pore complex-associated messenger RNA export machinery

Abstract

Theevolutionarily conserved protein Sem1/Dss1 is a subunit of the regulatory particle (RP) of the protea- some, and, in mammalian cells, binds the tumor suppressor protein BRCA2. Here, we describe a new function for yeast Semi. We show that sem 1 mutants are impaired in messenger RNA (mRNA) export and transcription elongation, and induce strong transcription-associated hyper- recombination phenotypes. Importantly, Semi, independent of the RP, is functionally linked to the mRNA export pathway. Biochemical analyses revealed that, in addition to the RP, Semi 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 Thpi, a TREX-2 component, to the NPC is perturbed in a sem 1 mutant. These findings reveal an unexpected nonprotea- somal function of Semi in mRNA export and in prevention of transcription-associated genome instability. Thus, Sem 1 is a versatile protein that might stabilize multiple protein complexes involved in diverse pathways. © 2009 Faza et al.