Nuclear pores mediate the transport of proteins and RNA between the nucleus and cytoplasm in a bi-directional fashion. While small molecules under 40Kda can diffuse larger molecules are actively transported through the pore. Genetic screens in yeast have identified mutations in genes, whose products influence the export of mRNA from the nucleus. We have used fission yeast Schizosaccharomyces pombe as a model system to study how eukaryotic cells export their mRNA out of the nucleus. Genetic approaches have identified genes that are functionally linked with mRNA export factor, Rae1p. We identified S. pombe mex67, (spmex67), through its interaction with rae1. spMex67p when expressed from a multicopy plasmid can suppress the growth and mRNA export defect of rael-167 ts phenotype. spMex67p is homologous to the S. cerevisiae scMex67p and to the human Tap protein. The spMex67p is 596 amino acids long, in contrast to S. cerevisiae, the spMex67p is not essential for growth and mRNA export. However, spMex67p plays an import role in mRNA export when mRNA export is inhibited due to partial loss of Rae1p function. spMex67p and Rae1p are genetically and functionally linked, rael-167 Dspmex67 are synthetically lethal. While expression of full length spMex67p from a multicopy plasmid is required to suppress the ts phenotype of rael-167, to suppress the growth and mRNA export defect of rael-167 Dspmex67 mutant only expression of 145- 505 amino acids is required. We found this domain in spMex67p, spMex67p (145-505), shuttles using novel import and export signals. It functions in mRNA export independent of the N-terminal and C-terminal regions that have been previously implicated in Tap/scMex67p, to contain nuclear import and export, nuclear pore localization, and the poly(A)+RNA binding domains. Taken together, our results suggest Rae1p and spMex67p likely functions in mRNA export in redundant reactions and that Mex67p utilizes more than one mechanism to export mRNA out of the nucleus. - Rae1p, spMex, p, mRNA Export, Nuclear pores, nuclear export signals, nuclear import signals, - Neither Human Subjects nor Human Tissues

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005643-09
Application #
6289134
Study Section
Special Emphasis Panel (BRL)
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code