title: A genome-wide function of THSC/TREX-2 at active genes prevents transcription-replication collisions.
abstract: The THSC/TREX-2 complex of Saccharomyces cerevisiae mediates the anchoring of transcribed genes to the nuclear pore, linking transcription elongation with mRNA export and genome stability, as shown for specific reporters. However, it is still unknown whether the function of TREX-2 is global and the reason for its relevant role in genome integrity. Here, by studying two TREX-2 representative subunits, Thp1 and Sac3, we show that TREX-2 has a genome-wide role in gene expression. Both proteins show similar distributions along the genome, with a gradient disposition at active genes that increases towards the 3' end. Thp1 and Sac3 have a relevant impact on the expression of long, G+C-rich and highly transcribed genes. Interestingly, replication impairment detected by the genome-wide accumulation of the replicative Rrm3 helicase is increased preferentially at highly expressed genes in the thp1Δ and sac3Δ mutants analyzed. Therefore, our work provides evidence of a function of TREX-2 at the genome-wide level and suggests a role for TREX-2 in preventing transcription-replication conflicts, as a source of genome instability derived from a defective messenger ribonucleoprotein particle (mRNP) biogenesis.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, 41092 Seville, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Santos-Pereira
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, 41092 Seville, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: García-Rubio
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, 41092 Seville, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: González-Aguilera
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, 41092 Seville, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Luna
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, 41092 Seville, Spain aguilo@us.es.
authors.forename: Andrés
authors.initials: A
authors.lastname: Aguilera
mesh_terms: D024509:3' Flanking Region; D004265:DNA Helicases / Q000378:metabolism; D004261:DNA Replication; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000378:metabolism*; D018272:Porins / Q000235:genetics / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D029543:Nucleocytoplasmic Transport Proteins; D018272:Porins; D012261:Ribonucleoproteins; C103382:SAC3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C476348:Thp1 protein, S cerevisiae; C459081:Rrm3 protein, S cerevisiae; D004265:DNA Helicases