Global analysis of eukaryotic mRNA degradation reveals Xrn1-dependent buffering of transcript levels

Mol Cell. 2013 Oct 10;52(1):52-62. doi: 10.1016/j.molcel.2013.09.010.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Cluster Analysis
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism*
  • Gene Expression Regulation, Fungal
  • Kinetics
  • Models, Genetic
  • Mutation
  • N-Glycosyl Hydrolases / metabolism
  • RNA Stability*
  • RNA, Fungal / biosynthesis
  • RNA, Fungal / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism*
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Substrate Specificity


  • Adaptor Proteins, Signal Transducing
  • Dcs2 protein, S cerevisiae
  • NRG1 protein, S cerevisiae
  • RNA, Fungal
  • RNA, Messenger
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Exoribonucleases
  • XRN1 protein, S cerevisiae
  • PAN3 protein, S cerevisiae
  • poly(A)-specific ribonuclease
  • DCS1 protein, S cerevisiae
  • N-Glycosyl Hydrolases