title: Transcriptome kinetics is governed by a genome-wide coupling of mRNA production and degradation: a role for RNA Pol II.
abstract: Transcriptome dynamics is governed by two opposing processes, mRNA production and degradation. Recent studies found that changes in these processes are frequently coordinated and that the relationship between them shapes transcriptome kinetics. Specifically, when transcription changes are counter-acted with changes in mRNA stability, transient fast-relaxing transcriptome kinetics is observed. A possible molecular mechanism underlying such coordinated regulation might lay in two RNA polymerase (Pol II) subunits, Rpb4 and Rpb7, which are recruited to mRNAs during transcription and later affect their degradation in the cytoplasm. Here we used a yeast strain carrying a mutant Pol II which poorly recruits these subunits. We show that this mutant strain is impaired in its ability to modulate mRNA stability in response to stress. The normal negative coordinated regulation is lost in the mutant, resulting in abnormal transcriptome profiles both with respect to magnitude and kinetics of responses. These results reveal an important role for Pol II, in regulation of both mRNA synthesis and degradation, and also in coordinating between them. We propose a simple model for production-degradation coupling that accounts for our observations. The model shows how a simple manipulation of the rates of co-transcriptional mRNA imprinting by Pol II may govern genome-wide transcriptome kinetics in response to environmental changes.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ophir
authors.initials: O
authors.lastname: Shalem
authors.forename: Bella
authors.initials: B
authors.lastname: Groisman
authors.forename: Mordechai
authors.initials: M
authors.lastname: Choder
authors.forename: Orna
authors.initials: O
authors.lastname: Dahan
authors.forename: Yitzhak
authors.initials: Y
authors.lastname: Pilpel
mesh_terms: D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D016681:Genome, Fungal; D006861:Hydrogen Peroxide / Q000633:toxicity; D007700:Kinetics; D012319:RNA Polymerase II / Q000235:genetics / Q000502:physiology*; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D013312:Stress, Physiological / Q000235:genetics; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D012319:RNA Polymerase II; C423309:RPB4 protein, S cerevisiae; C470553:RPB7 protein, S cerevisiae; C485634:RPO26 protein, S cerevisiae; D012321:DNA-Directed RNA Polymerases