title: New suppressors of THO mutations identify Thp3 (Ypr045c)-Csn12 as a protein complex involved in transcription elongation.
abstract: Formation of a ribonucleoprotein particle (mRNP) competent for export requires the coupling of transcription with mRNA processing and RNA export. A key link between these processes is provided by the THO complex. To progress in our understanding of this coupling, we have performed a search for suppressors of the transcription defect caused by the hpr1Δ mutation. This has permitted us to identify mutations in the genes for the RNA polymerase II mediator component Med10, the Sch9 protein kinase, and the Ypr045c protein. We report a role in transcription elongation for Ypr045c (Thp3) and the Csn12 component of the COP9 signalosome. Thp3 and Csn12 form a complex that is recruited to transcribed genes. Their mutations suppress the gene expression defects of THO complex mutants involved in mRNP biogenesis and export and show defects in mRNA accumulation. Transcription elongation impairment of thp3Δ mutants is shown by in vivo transcript run-on analysis performed in G-less systems. Thp3-Csn12 establishes a novel link between transcription and mRNA processing that opens new perspectives on our understanding of gene expression and reveals novel functions for a component of the COP9 signalosome. Thp3-Csn12 also copurifies with ribosomal proteins, which opens the possibility that it has other functions in addition to transcription.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Seville, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Jimeno
authors.forename: Cristina
authors.initials: C
authors.lastname: Tous
authors.forename: María L
authors.initials: ML
authors.lastname: García-Rubio
authors.forename: Michael
authors.initials: M
authors.lastname: Ranes
authors.forename: Cristina
authors.initials: C
authors.lastname: González-Aguilera
authors.forename: Antonio
authors.initials: A
authors.lastname: Marín
authors.forename: Andrés
authors.initials: A
authors.lastname: Aguilera
mesh_terms: D001483:Base Sequence; D000075686:COP9 Signalosome Complex; D004271:DNA, Fungal / Q000235:genetics; D005800:Genes, Fungal; D016681:Genome, Fungal; D056892:Mediator Complex / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016366:Open Reading Frames; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D013489:Suppression, Genetic; D014158:Transcription, Genetic
chemical_list: D004271:DNA, Fungal; C063494:HPR1 protein, S cerevisiae; D056892:Mediator Complex; D046912:Multiprotein Complexes; C113770:NUT2 protein, S cerevisiae; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; C026452:messenger ribonucleoprotein; D017346:Protein Serine-Threonine Kinases; C530964:SCH9 protein, S cerevisiae; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex