A Link between Secretion and Pre-mRNA Processing Defects in Saccharomyces cerevisiae and the Identification of a Novel Splicing Gene, RSE1

Abstract

ABSTRACT Secretory proteins in eukaryotic cells are transported to the cell surface via the endoplasmic reticulum (ER) and the Golgi apparatus by membrane-bounded vesicles. We screened a collection of temperature-sensitive mutants of Saccharomyces cerevisiae for defects in ER-to-Golgi transport. Two of the genes identified in this screen were PRP2 , which encodes a known pre-mRNA splicing factor, and RSE1 , a novel gene that we show to be important for pre-mRNA splicing. Both prp2-13 and rse1-1 mutants accumulate the ER forms of invertase and the vacuolar protease CPY at restrictive temperature. The secretion defect in each mutant can be suppressed by increasing the amount of SAR1 , which encodes a small GTPase essential for COPII vesicle formation from the ER, or by deleting the intron from the SAR1 gene. These data indicate that a failure to splice SAR1 pre-mRNA is the specific cause of the secretion defects in prp2-13 and rse1-1 . Moreover, these data imply that Sar1p is a limiting component of the ER-to-Golgi transport machinery and suggest a way that secretory pathway function might be coordinated with the amount of gene expression in a cell.