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.
Keywords: BRCA2; COP9; Dss1; Sem1; TREX-2; gene gating; genome instability; mRNA export; proteasome.