SM-like proteins function in mRNA degradation of Saccharomyces cerevisiae

Abstract

The degradation of mRNA is a critical step in determining the regulation and levels of gene expression. A family of Sm-Like (Lsm) proteins containing the "Sm" sequence motif has been identified, which forms a complex with U6 snRNA and functions in pre-mRNA splicing. Moreover, Lsm proteins interact with mRNA decay factors in yeast two-hybrid analysis. One of the Lsm proteins, Lsm1p, is required for the efficient decapping of mRNA during degradation. Lsm proteins might exist as a complex since they coimmunoprecipitate with each other. Based on these observations we hypothesized that the family of Lsm proteins might be involved in mRNA degradation. We showed that mutations in seven Lsm proteins (Lsm1-Lsm7) caused inhibition of decapping. These Lsm proteins co-immunoprecipitated with Dcp1p (the decapping enzyme), Pat1p (a decapping activator) and with mRNA, indicating that the Lsm proteins (Lsm1--Lsm7) play a direct role in promoting the decapping step of mRNA degradation. In addition, the Lsm proteins seem to form distinct complexes that affect different aspects of mRNA metabolism. A nuclear Lsm complex consisting of Lsm2p through Lsm8p, interacts with U6 snRNA and promotes pre-mRNA splicing. A cytoplasmic Lsm complex consisting of Lsm1p through Lsm7p binds mRNA and functions in mRNA degradation. The cytoplasmic Lsm complex plays a second role in protecting the 3 ' UTR of mRNA from trimming. Mutations in the cytoplasmic Lsm complex caused trimming of mRNAs. The ski mutations, which cause defects in 3' to 5' mRNA degradation suppressed the temperature-sensitive growth of lsm mutants by preventing the further degradation of trimmed mRNAs. These results argue that Lsm complex might bind to the 3' UTR of mRNAs and protect it from trimming. In addition, the 3' to 5 ' degradation of the trimmed mRNAs might at least in part account for the temperature-sensitive growth of the lsm and the pat1 mutants.