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Nucleic Acids Research, 1994, Vol. 22, No. 25 5555-5564
© 1994


Articles

The budding yeast U5 snRNP Prp8 is a highly conserved protein which links RNA splicing with cell cycle progression

Jacqueline E. Shea+, Jeremy H. Toyn and Leland H. Johnston*

Laboratory of Yeast Genetics, National Institute for Medical Research The Ridgeway, Mill Hill, London NW7 1AA, UK

*To whom correspondence should be addressed

+Present address: Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, UK

Received October 14, 1994. Revised November 18, 1994. Accepted November 18, 1994.

The dbf3 mutation was originally obtained In a screen for DNA synthesis mutants with a cell cycle phenotype in the budding yeast Saccharomyces cerevlslae. We have now isolated the DBFS gene and found It to be an essential gene with an ORF of 7239 nucleotldes, potentially encoding a large protein of 268 kDa. We also obtained an allele-specific high copy number suppressor of the dbf3-1 allele, encoded by the known SSB1 gene, a member of the Hsp70 family of heat shock proteins. The sequence of the Dbf3 protein is 58% identical over 2300 amino acid residues to a predicted protein from Caenorhabdltls elegans. Furthermore, partial sequences with 61% amino acid sequence Identity were deduced from two files of human cDNA in the EST nucleotlde database so that Dbf3 is a highly conserved protein. The nucleotlde sequence of DBF3 turned out to be Identical to the yeast gene PRP8, which encodes a U5 snRNP required for pre-mRNA splicing. This surprising result led us to further characterise the phenotype of dbf3 which confirmed its role in the cell cycle and showed It to function early, around the time of S phase. This data suggests a hitherto unexpected link between pre-mRNA splicing and the cell cycle.


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