title: The mRNA cap-binding protein Cbc1 is required for high and timely expression of genes by promoting the accumulation of gene-specific activators at promoters.
abstract: The highly conserved Saccharomyces cerevisiae cap-binding protein Cbc1/Sto1 binds mRNA co-transcriptionally and acts as a key coordinator of mRNA fate. Recently, Cbc1 has also been implicated in transcription elongation and pre-initiation complex (PIC) formation. Previously, we described Cbc1 to be required for cell growth under osmotic stress and to mediate osmostress-induced translation reprogramming. Here, we observe delayed global transcription kinetics in cbc1Δ during osmotic stress that correlates with delayed recruitment of TBP and RNA polymerase II to osmo-induced promoters. Interestingly, we detect an interaction between Cbc1 and the MAPK Hog1, which controls most gene expression changes during osmostress, and observe that deletion of CBC1 delays the accumulation of the activator complex Hot1-Hog1 at osmostress promoters. Additionally, CBC1 deletion specifically reduces transcription rates of highly transcribed genes under non-stress conditions, such as ribosomal protein (RP) genes, while having low impact on transcription of weakly expressed genes. For RP genes, we show that recruitment of the specific activator Rap1, and subsequently TBP, to promoters is Cbc1-dependent. Altogether, our results indicate that binding of Cbc1 to the capped mRNAs is necessary for the accumulation of specific activators as well as PIC components at the promoters of genes whose expression requires high and rapid transcription.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Dr. Moliner 50, Burjassot 46100, Spain; ERI Biotecmed. Universitat de València, Dr. Moliner 50, Burjassot 46100, Spain.
authors.forename: Tianlu
authors.initials: T
authors.lastname: Li
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Dr. Moliner 50, Burjassot 46100, Spain.
authors.forename: Nikki
authors.initials: N
authors.lastname: De Clercq
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Dr. Moliner 50, Burjassot 46100, Spain; ERI Biotecmed. Universitat de València, Dr. Moliner 50, Burjassot 46100, Spain.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Medina
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Dr. Moliner 50, Burjassot 46100, Spain; Department of Chemistry and Molecular Biology, University of Göteborg, Box 452, S-405 30 Göteborg, Sweden.
authors.forename: Elena
authors.initials: E
authors.lastname: Garre
authors.affiliation: Department of Chemistry and Molecular Biology, University of Göteborg, Box 452, S-405 30 Göteborg, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Sunnerhagen
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Dr. Moliner 50, Burjassot 46100, Spain; ERI Biotecmed. Universitat de València, Dr. Moliner 50, Burjassot 46100, Spain.
authors.forename: José E
authors.initials: JE
authors.lastname: Pérez-Ortín
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Dr. Moliner 50, Burjassot 46100, Spain; ERI Biotecmed. Universitat de València, Dr. Moliner 50, Burjassot 46100, Spain. Electronic address: paula.alepuz@uv.es.
authors.forename: Paula
authors.initials: P
authors.lastname: Alepuz
mesh_terms: D015966:Gene Expression Regulation, Fungal; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D009997:Osmotic Pressure; D039381:RNA Cap-Binding Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D061785:Transcription Initiation, Genetic; D014158:Transcription, Genetic
chemical_list: C120535:HOT1 protein, S cerevisiae; D009687:Nuclear Proteins; D039381:RNA Cap-Binding Proteins; D012333:RNA, Messenger; C101398:STO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases
keywords: Cap-binding protein; Cbc1/Sto1/Cbp80; Osmotic stress; RNAPII transcription; Ribosomal genes