The Saccharomyces cerevisiae gene CDC40/PRP17 controls cell cycle progression through splicing of the ANC1 gene.
The timing of events in the cell cycle is of crucial importance, as any error can lead to cell death or cancerous growth. This accurate timing is accomplished through the activation of specific CDC genes. Mutations in the CDC40/PRP17 gene cause cell cycle arrest at the G2/M stage. It was previously found that the CDC40 gene encodes a pre-mRNA splicing factor, which participates in the second step of the splicing reaction. In this paper we dissect the mechanism by which pre-mRNA splicing affects cell cycle progression. We identify ANC1 as the target of CDC40 regulation. Deletion of the ANC1 intron relieves the cell cycle arrest and temperature sensitivity of cdc40 mutants. Furthermore, we identify, through point mutation analysis, specific residues in the ANC1 intron that are important for its splicing dependency on Cdc40p. Our results demonstrate a novel mechanism of cell cycle regulation that relies on the differential splicing of a subset of introns by specific splicing factors.
Dahan
Orna
O
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
Kupiec
Martin
M
D000483:Alleles; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D025141:Drug Resistance, Fungal / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics; D007438:Introns / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics*; D000072260:RNA Splicing Factors; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D013696:Temperature; D035362:Transcription Factor TFIID / Q000235:genetics*
C093570:CDC40 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D012322:RNA Precursors; D022821:RNA Splice Sites; D000072260:RNA Splicing Factors; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C090313:TAF14 protein, S cerevisiae; D035362:Transcription Factor TFIID; D003300:Copper