Role of PKA in protein translation regulation during adverse environmental growth conditions.

PAULA PORTELA

Conferencia; LIV Reunión Anual SAIB; 2018

In response to environmental stress conditions, the cellular protein content is readjusted through signalling pathways, such as cAMP-PKA, that alter different processes connected to transcriptional, translational and post-translational programs. In S. cerevisiae, PKA is a hetero-tetramer composed of two regulatory subunits encoded by BCY1 gene, and two catalytic subunits encoded by three genes, TPK1, TPK2 and TPK3. We reported that Tpk2 and Tpk3 differently localize to both mRNA processing bodies (PBs) and stress granules (SGs) in response to glucose starvation, to strong but not mild osmotic stress, to the severity of heat stress and stationary phase. Deletion of TPK3 or TPK2 genes differentially impacts on the capacity of cells to form PBs or SGs, the global translation and translational fitness of specific mRNAs. We also found that Tpk2 and Tpk3 showed different dynamics and mechanisms of interaction with SGs and PBs. Moreover, Tpk2 and Tpk3 kinase activity and Tpk2 Q-rich domain are involved in the mechanism of assembly of PBs and SGs in a stress type-dependent manner. A global characterization of granular enriched fraction from mild and severe heat stress showed different protein composition in both conditions. The results suggest that Tpk2 and Tpk3 localized in PBs/SGs could interact with a complex network of distinct protein and potential substrates. Our findings contribute to the concept that different stress conditions induce specific cellular responses, and highlight a different potential role for each isoform of PKA on fundamental processes such as the synthesis of proteins.