Mutations in genes of Saccharomyces cerevisiae encoding pre-mRNA splicing factors cause cell cycle arrest through activation of the spindle checkpoint.
Previous work has identified a group of genes whose products play important roles in two seemingly unrelated processes: cell cycle progression and splicing. The products of these genes show a network of physical and genetic interactions suggestive of the existence of a protein complex, the cell cycle and splicing complex (CSC). Here we analyze the genetic interactions between ISY1, SYF2 and NTC20, three non-essential components of the CSC. We show that mutations in ISY1 cause lethality in the absence of Ntc20p, and that the double mutant isy1Delta syf2Delta shows a temperature-dependent cell cycle arrest. This arrest is due to lower levels of alpha-tubulin, a protein encoded by TUB1 and TUB3, two intron-containing genes. We show that the low levels of alpha-tubulin in isy1Delta syf2Delta trigger activation of the spindle checkpoint, causing cell cycle arrest. Thus, our results have uncovered an unexpected role for pre-mRNA splicing in the maintenance of the fidelity of chromosome transmission during cell division.
Dahan
Orna
O
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
Kupiec
Martin
M
D001692:Biological Transport; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005800:Genes, Fungal; D008870:Microtubules / Q000187:drug effects; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D010641:Phenotype; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing; D000072260:RNA Splicing Factors; D012331:RNA, Fungal / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D013696:Temperature; D014404:Tubulin / Q000096:biosynthesis / Q000235:genetics
C093570:CDC40 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D012322:RNA Precursors; D000072260:RNA Splicing Factors; D012331:RNA, Fungal; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014404:Tubulin; D015739:Nocodazole