Abstract
During the cell cycle, the levels of hundreds of mRNAs change in a periodic manner, but how this is achieved by alterations in the rates of mRNA synthesis and degradation has not been studied systematically. Here, we used metabolic RNA labeling and comparative dynamic transcriptome analysis (cDTA) to derive mRNA synthesis and degradation rates every 5min during three cell cycle periods of the yeast Saccharomyces cerevisiae. A novel statistical model identified 479 genes that show periodic changes in mRNA synthesis and generally also periodic changes in their mRNA degradation rates. Peaks of mRNA degradation generally follow peaks of mRNA synthesis, resulting in sharp and high peaks of mRNA levels at defined times during the cell cycle. Whereas the timing of mRNA synthesis is set by upstream DNA motifs and their associated transcription factors (TFs), the synthesis rate of a periodically expressed gene is apparently set by its core promoter.
Highlights
The eukaryotic cell cycle is controlled by periodic gene expression
We investigated the influence of cell cycle regulating transcription factors (TFs) on the mRNA synthesis of their target genes
To investigate the potential role of mRNA degradation rate changes quantitatively, we extended the DTA method such that it allows for the estimation of changes in mRNA synthesis and degradation rates
Summary
Gene expression changes during the cell cycle have been studied extensively in the budding yeast Saccharomyces cerevisiae (Wittenberg & Reed, 2005), and in the fission yeast Schizosaccharomyces pombe. These studies have revealed transcriptional regulatory proteins that drive cell cycle progression, their DNA-binding motifs, and their target genes (Simon et al, 2001; Lee et al, 2002; Pramila et al, 2006). Parts of the regulatory networks that drive periodic gene expression could be reverse engineered (Wu et al, 2006; Hu et al, 2007). A model suggesting the coupling of a TF network to CDK activity for robust oscillations in the cell cycle has been proposed (Kovacs et al, 2012)
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