Control of signaling in a MAP-kinase pathway by an RNA-binding protein.
Signaling-protein mRNAs tend to have long untranslated regions (UTRs) containing binding sites for RNA-binding proteins regulating gene expression. Here we show that a PUF-family RNA-binding protein, Mpt5, represses the yeast MAP-kinase pathway controlling differentiation to the filamentous form. Mpt5 represses the protein levels of two pathway components, the Ste7 MAP-kinase kinase and the Tec1 transcriptional activator, and negatively regulates the kinase activity of the Kss1 MAP kinase. Moreover, Mpt5 specifically inhibits the output of the pathway in the absence of stimuli, and thereby prevents inappropriate cell differentiation. The results provide an example of what may be a genome-scale level of regulation at the interface of signaling networks and protein-RNA binding networks.
Prinz
Susanne
S
Institute for Systems Biology, Seattle, Washington, United States of America.
Aldridge
Christine
C
Ramsey
Stephen A
SA
Taylor
R James
RJ
Galitski
Timothy
T
D002448:Cell Adhesion; D048430:Cell Shape; D004268:DNA-Binding Proteins / Q000502:physiology; D025461:Feedback, Physiological; D015966:Gene Expression Regulation, Fungal / Q000235:genetics / Q000502:physiology*; D005800:Genes, Fungal; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010641:Phenotype; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
D004268:DNA-Binding Proteins; C449502:MPT5 protein, S cerevisiae; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C069926:TEC1 protein, S cerevisiae; D014157:Transcription Factors; D011494:Protein Kinases; C541984:KSS1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C119844:STE7 protein, S cerevisiae