title: Sem1 is a functional component of the nuclear pore complex-associated messenger RNA export machinery.
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.
authors.affiliation: Institute of Biochemistry, ETH Zürich, Zürich, Switzerland.
authors.forename: Marius Boulos
authors.initials: MB
authors.lastname: Faza
authors.forename: Stefan
authors.initials: S
authors.lastname: Kemmler
authors.forename: Sonia
authors.initials: S
authors.lastname: Jimeno
authors.forename: Cristina
authors.initials: C
authors.lastname: González-Aguilera
authors.forename: Andrés
authors.initials: A
authors.lastname: Aguilera
authors.forename: Ed
authors.initials: E
authors.lastname: Hurt
authors.forename: Vikram Govind
authors.initials: VG
authors.lastname: Panse
mesh_terms: D021581:Active Transport, Cell Nucleus; D000075686:COP9 Signalosome Complex; D003564:Cytidine Deaminase / Q000378:metabolism; D004271:DNA, Fungal / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D042822:Genomic Instability; D005838:Genotype; D046912:Multiprotein Complexes / Q000378:metabolism; D009154:Mutation; D022022:Nuclear Pore / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D034443:RNA Transport; D012331:RNA, Fungal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D012261:Ribonucleoproteins / Q000378:metabolism; D004718:Saccharomycetales / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004271:DNA, Fungal; D004277:DNA, Single-Stranded; D005656:Fungal Proteins; D046912:Multiprotein Complexes; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex; D046988:Proteasome Endopeptidase Complex; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; C119011:26S proteasome non-ATPase regulatory subunit 13