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Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
PKA isoforms coordinate mRNA fate during nutrient starvation
Vanesa Tudisca1, Clare Simpson, Lydia Castelli
1Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Journal of Cell Science
|August 18, 2012
Summary
The protein kinase A (PKA) pathway regulates mRNA silencing foci formation and translation arrest during cellular stress. This pathway coordinates mRNA fate with the cell's nutritional status and growth phase.
Area of Science:
- Molecular Biology
- Cellular Stress Response
- Yeast Genetics
Background:
- Stress conditions induce mRNA and protein aggregation into silencing foci, but underlying signaling pathways remain unclear.
- Protein kinase A (PKA) catalytic isoforms Tpk2 and Tpk3 were previously shown to localize with processing and stress bodies in Saccharomyces cerevisiae.
Purpose of the Study:
- To elucidate the role of PKA in mRNA silencing foci formation and translation regulation under stress.
- To investigate the interaction of PKA isoforms with translation factors and their dynamic changes during glucose starvation.
Main Methods:
- Co-immunoprecipitation to assess protein interactions.
- Microscopy to visualize foci formation in yeast mutants.
- Analysis of gene deletion mutants (TPK2, TPK3) under various growth conditions.
Main Results:
- Tpk2 and Tpk3 associate with translation initiation factors Pab1 and Rps3 in growing cells.
- Glucose starvation disrupts Tpk-initiation factor interaction, leading to accumulation in processing bodies.
- TPK2 or TPK3 deletion impairs granule formation and translation arrest during starvation and stationary phase.
- PKA influences Rpg1 and eIF4G(1) protein levels, suggesting control over cap-dependent translation.
Conclusions:
- The PKA pathway is crucial for coordinating mRNA fate, including silencing and translation, in response to nutritional cues and growth status.
- PKA acts as a central regulator linking environmental signals to mRNA processing and localization in yeast.
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