The fission yeast Schizosaccharmyces pombe has been utilized as a model system to study nucleocytoplasmic transport of mRNA. A temperature (ts) sensitive mutant rae1-1 (ribonucleic acid export) is defective in the nuclear export of polyA+ RNA when grown at restrictive temperature. The rae1 protein is a member of the WD-40 repeat protein family. It appears to be primarily located in the cytoplasm around the nuclear membrane. The rae1 gene product is required not only for mRNA export but is also essential for cell cycle progression, particularly at the G2/M boundary. Nucleocytoplasmic transport of proteins is thought to be required for cell cycle progression in many systems. By analogy rae1 function may not only be required for nuclear export of mRNA but also for shuttling proteins, some which may be required for cell cycle progression. A number of extragenic and multicopy suppressors of rae1-1 mutant were isolated that allowed growth and mRNA export at restricted temperatures. Of these, rad24 (roe3) was isolated as an extragenic suppressor, and skp1 (glycogen synthase kinase-3) and ptc1 (protein phosphatase 2c) were isolated as multicopy suppressors. Importantly, genetic interactions of rae1 with other rae1-1 suppressor mutant strains resulted in the identification of additional mRNA export genes, such as rad24 and heat shock protein Hsp90 (swo1). Both rad24 and Hsp90 mutant strains showed mRNA export defects at 36 degrees C. Studies with rael-1, rad24 and Hsp90 mutant strains suggested these genes were not only required for nuclear export of mRNA but also for cell cycle progression. These results suggest a potential link between nuclear export and cell cycle progression, particularly at the G2/M boundary.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005643-05
Application #
5201528
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code