RT Journal
A1 Sun, Mai
A1 Schwalb, Björn
A1 Schulz, Daniel
A1 Pirkl, Nicole
A1 Etzold, Stefanie
A1 Larivière, Laurent
A1 Maier, Kerstin C.
A1 Seizl, Martin
A1 Tresch, Achim
A1 Cramer, Patrick
T1 Comparative dynamic transcriptome analysis (cDTA) reveals mutual feedback between mRNA synthesis and degradation
JF Genome Research 
JO Genome Research 
YR 2012 
FD July 01 
VO 22 
IS 7 
SP 1350 
OP 1359 
DO 10.1101/gr.130161.111 
UL http://genome.cshlp.org/content/22/7/1350.abstract 
AB To monitor eukaryotic mRNA metabolism, we developed comparative dynamic transcriptome analysis (cDTA). cDTA provides absolute rates of mRNA synthesis and decay in Saccharomyces cerevisiae (Sc) cells with the use of Schizosaccharomyces pombe (Sp) as an internal standard. cDTA uses nonperturbing metabolic labeling that supersedes conventional methods for mRNA turnover analysis. cDTA reveals that Sc and Sp transcripts that encode orthologous proteins have similar synthesis rates, whereas decay rates are fivefold lower in Sp, resulting in similar mRNA concentrations despite the larger Sp cell volume. cDTA of Sc mutants reveals that a eukaryote can buffer mRNA levels. Impairing transcription with a point mutation in RNA polymerase (Pol) II causes decreased mRNA synthesis rates as expected, but also decreased decay rates. Impairing mRNA degradation by deleting deadenylase subunits of the Ccr4–Not complex causes decreased decay rates as expected, but also decreased synthesis rates. Extended kinetic modeling reveals mutual feedback between mRNA synthesis and degradation that may be achieved by a factor that inhibits synthesis and enhances degradation.