KSRP and β-Catenin mRNA Decay
Author Information
Author(s): Gherzi Roberto, Trabucchi Michele, Ponassi Marco, Ruggiero Tina, Corte Giorgio, Moroni Christoph, Chen Ching-Yi, Khabar Khalid S, Andersen Jens S, Briata Paola
Primary Institution: Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
Hypothesis
KSRP is required for the decay of β-catenin mRNA and is inactivated by PI3K-AKT signaling.
Conclusion
The study reveals that KSRP is crucial for the rapid degradation of β-catenin mRNA, and its phosphorylation by AKT signaling impairs this function.
Supporting Evidence
- β-catenin mRNA is labile and its half-life is prolonged by Wnt and PI3K-AKT signaling.
- KSRP is a major determinant of β-catenin mRNA instability.
- AKT phosphorylates KSRP, impairing its ability to promote mRNA decay.
- Insulin-induced AKT activation stabilizes β-catenin mRNA.
- KSRP knockdown leads to increased β-catenin mRNA levels.
- Phosphorylated KSRP interacts with 14-3-3, affecting its decay-promoting activity.
- AKT activation impairs KSRP's interaction with the exosome.
Takeaway
KSRP helps break down a specific type of RNA that controls cell growth, and when a certain signal is turned on, it stops working, allowing the RNA to stick around longer.
Methodology
The study used RT-PCR and microarray analysis to assess mRNA stability and decay rates in response to various treatments.
Digital Object Identifier (DOI)
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