6533b835fe1ef96bd129f5af
RESEARCH PRODUCT
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
Daniel A. MedinaNikki De ClercqPer SunnerhagenElena GarreJosé E. Pérez-ortínPaula AlepuzTianlu Lisubject
0301 basic medicineTBX1Saccharomyces cerevisiae ProteinsTranscription GeneticBiophysicsRNA polymerase IISaccharomyces cerevisiaeBiochemistry03 medical and health sciencesOsmotic PressureStructural BiologyTranscription (biology)Gene Expression Regulation FungalGene expressionGeneticsRNA MessengerMolecular BiologyTranscription factorTranscription Initiation GeneticbiologyActivator (genetics)Nuclear ProteinsPromoterMolecular biology030104 developmental biologyRNA Cap-Binding Proteinsbiology.proteinMitogen-Activated Protein KinasesCREB1Transcription Factorsdescription
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.
year | journal | country | edition | language |
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2015-10-02 | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms |