Regulated mRNA stability of the Cdk inhibitor Rum1 links nutrient status to cell cycle progression.
BACKGROUND
The survival of a cell depends on continuous sensing of the nutritional environment and appropriate coordination of the cell cycle. The fission yeast Schizosaccharomyces pombe is an excellent model system in which to study these processes. In the presence of nutrients, fission yeast cells grow and divide, spending most of their time in G2; when nutrients are limiting, they are promoted into mitosis and arrest the cell cycle in G1. The molecular mechanisms underlying this response are currently unknown.


RESULTS
Here, we show that expression of the fission yeast Cdk inhibitor Rum1, a key regulator of Cdc2/cyclin B in G1, is subject to regulated mRNA stability in response to nutrient deprivation. In complete minimal medium, rum1 mRNAs are very unstable. Following nitrogen starvation, rum1 mRNAs are rapidly stabilized, allowing the accumulation of Rum1 protein to delay the G1 phase of the subsequent cell cycle. Instability of rum1 mRNAs in complete minimal medium depends on the presence of AU-rich elements in the 3'UTR. We also show that lack of this mechanism has consequences in the mitotic cell cycle, in meiosis, and in the control of ploidy.


CONCLUSIONS
We propose that mRNA stability is an important mechanism to fine tune the expression of the rum1 gene, in order to allow the production of appropriate levels of Rum1 protein in response to changes in the nutritional environment.
Daga
Rafael R
RR
Instituto de Microbiología Bioquímica, Universidad de Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain.
Bolaños
Pilar
P
Moreno
Sergio
S
D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D016193:G1 Phase; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D009154:Mutation; D009584:Nitrogen / Q000172:deficiency*; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000502:physiology; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
D012333:RNA, Messenger; C086077:Rum1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D009584:Nitrogen