title: The THP1-SAC3-SUS1-CDC31 complex works in transcription elongation-mRNA export preventing RNA-mediated genome instability.
abstract: The eukaryotic THO/TREX complex, involved in mRNP biogenesis, plays a key role in the maintenance of genome integrity in yeast. mRNA export factors such as Thp1-Sac3 also affect genome integrity, but their mutations have other phenotypes different from those of THO/TREX. Sus1 is a novel component of SAGA transcription factor that also associates with Thp1-Sac3, but little is known about its effect on genome instability and transcription. Here we show that Thp1, Sac3, and Sus1 form a functional unit with a role in mRNP biogenesis and maintenance of genome integrity that is independent of SAGA. Importantly, the effects of ribozyme-containing transcription units, RNase H, and the action of human activation-induced cytidine deaminase on transcription and genome instability are consistent with the possibility that R-loops are formed in Thp1-Sac3-Sus1-Cdc31 as in THO mutants. Our data reveal that Thp1-Sac3-Sus1-Cdc31, together with THO/TREX, define a specific pathway connecting transcription elongation with export via an RNA-dependent dynamic process that provides a feedback mechanism for the control of transcription and the preservation of genetic integrity of transcribed DNA regions.
authors.affiliation: Centro Andaluz de Biologia Molecular y Medicina Regenerativa, Universidad de Sevilla-CSIC, 41092 Sevilla, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: González-Aguilera
authors.forename: Cristina
authors.initials: C
authors.lastname: Tous
authors.forename: Belén
authors.initials: B
authors.lastname: Gómez-González
authors.forename: Pablo
authors.initials: P
authors.lastname: Huertas
authors.forename: Rosa
authors.initials: R
authors.lastname: Luna
authors.forename: Andrés
authors.initials: A
authors.lastname: Aguilera
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000378:metabolism; D004252:DNA Mutational Analysis; D042822:Genomic Instability; D006801:Humans; D008954:Models, Biological; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins; D010641:Phenotype; D018272:Porins; D016337:RNA, Catalytic / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: C083769:CDC31 protein, S cerevisiae; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D018272:Porins; D016337:RNA, Catalytic; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C103382:SAC3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C481300:Sus1 protein, S cerevisiae; C476348:Thp1 protein, S cerevisiae; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase