title: Global analysis of eukaryotic mRNA degradation reveals Xrn1-dependent buffering of transcript levels.
abstract: The rates of mRNA synthesis and degradation determine cellular mRNA levels and can be monitored by comparative dynamic transcriptome analysis (cDTA) that uses nonperturbing metabolic RNA labeling. Here we present cDTA data for 46 yeast strains lacking genes involved in mRNA degradation and metabolism. In these strains, changes in mRNA degradation rates are generally compensated by changes in mRNA synthesis rates, resulting in a buffering of mRNA levels. We show that buffering of mRNA levels requires the RNA exonuclease Xrn1. The buffering is rapidly established when mRNA synthesis is impaired, but is delayed when mRNA degradation is impaired, apparently due to Xrn1-dependent transcription repressor induction. Cluster analysis of the data defines the general mRNA degradation machinery, reveals different substrate preferences for the two mRNA deadenylase complexes Ccr4-Not and Pan2-Pan3, and unveils an interwoven cellular mRNA surveillance network.
authors.affiliation: Gene Center Munich and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.
authors.forename: Mai
authors.initials: M
authors.lastname: Sun
authors.forename: Björn
authors.initials: B
authors.lastname: Schwalb
authors.forename: Nicole
authors.initials: N
authors.lastname: Pirkl
authors.forename: Kerstin C
authors.initials: KC
authors.lastname: Maier
authors.forename: Arne
authors.initials: A
authors.lastname: Schenk
authors.forename: Henrik
authors.initials: H
authors.lastname: Failmezger
authors.forename: Achim
authors.initials: A
authors.lastname: Tresch
authors.forename: Patrick
authors.initials: P
authors.lastname: Cramer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D016000:Cluster Analysis; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D007700:Kinetics; D008957:Models, Genetic; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D020871:RNA Stability; D012331:RNA, Fungal / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005095:Exoribonucleases; D009699:N-Glycosyl Hydrolases; D012331:RNA, Fungal; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C487769:Dcs2 protein, S cerevisiae; C117881:NRG1 protein, S cerevisiae; C068398:XRN1 protein, S cerevisiae; C101747:PAN3 protein, S cerevisiae; C478395:DCS1 protein, S cerevisiae