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Sem1 is a functional component of the nuclear pore complex–associated messenger RNA export machinery

¹ Institute of Biochemistry, ETH Zürich, CH-8093 Zürich, Switzerland
² Molecular Life Sciences Program, Life Sciences Zurich, CH-8057 Zurich, Switzerland
³ Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Sevilla, Spain
⁴ Biochemie-Zentrum Heidelberg, Universität Heidelberg, D-69120 Heidelberg, Germany

Correspondence to Vikram Govind Panse: vikram.panse{at}bc.biol.ethz.ch

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.

Abbreviations used in this paper: 5-FOA, 5-fluoroorotic acid; AID, activation-induced cytidine deaminase; ChIP, chromatin immunoprecipitation; CSN, COP9 signalosome; DSB, double-strand break; GANP, germinal center–associated nuclear protein; mRNP, messenger ribonucleoprotein; NPC, nuclear pore complex; PCI, proteasome-COP9-initiation factor; RNAPII, RNA polymerase II; RP, regulatory particle; se, synthetic enhanced; sl, synthetic lethal; ssDNA, single-stranded DNA; TAP, tandem affinity purification; TAR, transcription-associated recombination; TEV, tobacco etch viral protease; TREX, transcription export.

© 2009 Faza et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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