Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast.
The eukaryotic cell cycle is driven by a cascade of cyclins and kinase partners including the G1 cyclin Cln3p in yeast. As the first step in this cascade, Cln3p is uniquely positioned to determine the critical growth-rate threshold for division. To analyze factors regulating CLN3 expression, we identified a short upstream open reading frame (uORF) in the 5' leader of CLN3 mRNA as a translational control element. This control element is critical for the growth-dependent regulation of Cln3p synthesis because it specifically represses CLN3 expression during conditions of diminished protein synthesis or slow growth. Inactivation of the uORF accelerates the completion of Start and entry into the cell cycle suggesting that translational regulation of CLN3 provides a mechanism coupling cell growth and division.
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MGH Cancer Center, Massachusetts General Hospital, Charlestown 02129, USA.
Schmidt
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D000935:Antifungal Agents / Q000494:pharmacology; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D017930:Genes, Reporter; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics; D010448:Peptide Initiation Factors / Q000235:genetics; D011090:Polyenes / Q000494:pharmacology; D011132:Polyribosomes / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D017422:Sequence Analysis, DNA; D020123:Sirolimus
D000935:Antifungal Agents; C079895:CLN3 protein, S cerevisiae; D016213:Cyclins; D005656:Fungal Proteins; D010448:Peptide Initiation Factors; D011090:Polyenes; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus