Analysis of Processing Bodies Assembly and mRNA Decay

Abstract

Translation and mRNA degradation are tightly regulated upon stress where protein synthesis and mRNA decay are modulated to optimize the stress response. However, the mechanisms that regulate mRNA decay and translation during stress are not fully understood. In this thesis, I show that Dcp2, a major decapping enzyme, undergoes phosphorylation by Ste20 kinase during stress and promotes stabilization of ribosomal protein mRNAs as well as Dcp2 accumulation in Processing bodies (P-bodies) in Saccharomyces cerevisiae. In addition, I have analyzed the role of P-bodies by examining how alterations in P-body assembly factors affect the transcriptome. Interestingly, I observe that Edc3, a component of P-bodies that promotes their assembly, can either stabilize or destabilize specific subsets of yeast mRNAs. I also show that Lsm4, a P-body component that mediates the assembly of P-bodies along with Edc3, promotes mRNA decay via its aggregation domain. These results argue that P-bodies can function as sites of mRNA degradation and storage for a subset of mRNAs by the localized accumulation of specific factors.