Phosphorylation of an RNA-Binding Protein Rck/Me31b by Hippo Is Essential for Adipose Tissue Aging

Area of Science:

• Molecular Biology
• Genetics
• Aging Research

Background:

• Metazoan lifespan is influenced by signaling networks regulating metabolism and stress.
• Key regulators include insulin/IGF-1, AMPK, mTOR, and sirtuins.
• The Hippo/Mammalian Ste20-like Kinase1 (MST1) pathway's role in higher organisms' lifespan is unexplored.

Purpose of the Study:

• To investigate the role of the Hippo/MST1 pathway in lifespan regulation in higher metazoans.
• To elucidate the molecular mechanisms by which Hpo/MST1 affects lifespan, lipid metabolism, and gene expression.

Main Methods:

• Overexpression and RNA interference (RNAi) of the Hpo gene in Drosophila melanogaster.
• Analysis of lipid metabolism, aging-associated gene expression, and mRNA stability.
• Studies in mouse adipocytes to examine Hpo/Mst1's role in adipogenesis and RNA-binding protein interactions.

Main Results:

• Hpo overexpression decreased lifespan in Drosophila, while Hpo depletion increased lifespan.
• These effects were linked to Hpo-induced transcriptional activation of Me31b/RCK, stabilizing Akh mRNA.
• Hpo/Mst1 mediated adipocyte differentiation and regulated RNA-binding proteins and mRNA stability in mouse adipocytes.

Conclusions:

• The Hippo/MST1 pathway plays a conserved role in regulating lifespan across metazoans.
• Hpo/MST1 influences longevity by modulating adipogenesis and fatty acid metabolism.
• The pathway's effects are mediated through the regulation of specific RNA-binding proteins and target mRNAs.