Genetic and physical interactions between factors involved in both cell cycle progression and pre-mRNA splicing in Saccharomyces cerevisiae.
The PRP17/CDC40 gene of Saccharomyces cerevisiae functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. The Prp17/Cdc40 protein participates in the second step of the splicing reaction and, in addition, prp17/cdc40 mutant cells held at the restrictive temperature arrest in the G2 phase of the cell cycle. Here we describe the identification of nine genes that, when mutated, show synthetic lethality with the prp17/cdc40Delta allele. Six of these encode known splicing factors: Prp8p, Slu7p, Prp16p, Prp22p, Slt11p, and U2 snRNA. The other three, SYF1, SYF2, and SYF3, represent genes also involved in cell cycle progression and in pre-mRNA splicing. Syf1p and Syf3p are highly conserved proteins containing several copies of a repeated motif, which we term RTPR. This newly defined motif is shared by proteins involved in RNA processing and represents a subfamily of the known TPR (tetratricopeptide repeat) motif. Using two-hybrid interaction screens and biochemical analysis, we show that the SYF gene products interact with each other and with four other proteins: Isy1p, Cef1p, Prp22p, and Ntc20p. We discuss the role played by these proteins in splicing and cell cycle progression.
Ben-Yehuda
S
S
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
Dix
I
I
Russell
C S
CS
McGarvey
M
M
Beggs
J D
JD
Kupiec
M
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D053487:DEAD-box RNA Helicases; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016195:G2 Phase / Q000235:genetics; D005800:Genes, Fungal; D006801:Humans; D008969:Molecular Sequence Data; D020365:RNA Helicases; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing / Q000235:genetics*; D000072260:RNA Splicing Factors; D012331:RNA, Fungal / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000235:genetics; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D017381:Spliceosomes / Q000235:genetics
C093570:CDC40 protein, S cerevisiae; C513239:CEF1 protein, S cerevisiae; C419763:CLF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C118319:ISY1 protein, S cerevisiae; D012322:RNA Precursors; D000072260:RNA Splicing Factors; D012331:RNA, Fungal; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C419764:Syf1 protein, S cerevisiae; C405484:U2 small nuclear RNA; C067135:PRP22 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases