title: Genome-wide function of THO/TREX in active genes prevents R-loop-dependent replication obstacles.
abstract: THO/TREX is a conserved nuclear complex that functions in mRNP biogenesis and prevents transcription-associated recombination. Whether or not it has a ubiquitous role in the genome is unknown. Chromatin immunoprecipitation (ChIP)-chip studies reveal that the Hpr1 component of THO and the Sub2 RNA-dependent ATPase have genome-wide distributions at active ORFs in yeast. In contrast to RNA polymerase II, evenly distributed from promoter to termination regions, THO and Sub2 are absent at promoters and distributed in a gradual 5' → 3' gradient. This is accompanied by a genome-wide impact of THO-Sub2 deletions on expression of highly expressed, long and high G+C-content genes. Importantly, ChIP-chips reveal an over-recruitment of Rrm3 in active genes in THO mutants that is reduced by RNaseH1 overexpression. Our work establishes a genome-wide function for THO-Sub2 in transcription elongation and mRNP biogenesis that function to prevent the accumulation of transcription-mediated replication obstacles, including R-loops.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, Sevilla, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Gómez-González
authors.forename: María
authors.initials: M
authors.lastname: García-Rubio
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Bermejo
authors.forename: Hélène
authors.initials: H
authors.lastname: Gaillard
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Antonio
authors.initials: A
authors.lastname: Marín
authors.forename: Marco
authors.initials: M
authors.lastname: Foiani
authors.forename: Andrés
authors.initials: A
authors.lastname: Aguilera
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004271:DNA, Fungal / Q000737:chemistry; D016681:Genome, Fungal; D009687:Nuclear Proteins / Q000378:metabolism*; D011995:Recombination, Genetic; D012261:Ribonucleoproteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004271:DNA, Fungal; C063494:HPR1 protein, S cerevisiae; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; C026452:messenger ribonucleoprotein; D000251:Adenosine Triphosphatases; C027900:RNA-dependent ATPase