[PhD Thesis Presentation] - Mr. Shohei Takaoka " Role of 5’ - 3’ exoribonuclease Xrn1 in energy expenditure and control of obesity"

Presenter: Mr. Shohei Takaoka

Supervisor: Professor Tadashi Yamamoto

Co-Supervisor: Professor Hiroaki Kitano

Unit: Cell Signal Unit

Title: Role of 5’ - 3’ exoribonuclease Xrn1 in energy expenditure and control of obesity

Abstract:

Gene expression of eukaryotes is regulated by various processes including mRNA degradation. Dysregulation of mRNA degradation is now considered to be possible cause of various disease including cancer, neurodegenerative disease, diabetes and obesity.
5’ - 3’ exoribonuclease Xrn1 functions at the last step of mRNA degradation. Recent studies showed that Xrn1 forms specific cytoplasmic messenger ribonucleoprotein (mRNP) granules in post-synapse to regulate local translation in neuron. However, there are no physiological studies that have investigated the function of Xrn1 in brain. Therefore, I generated brain-specific Xrn1 knockout mice for the first time and analyzed their phenotype. Interestingly, the knockout mice showed obesity and hyperphagia. Moreover, I found that dysregulated expression of appetite and energy homeostasis related genes in hypothalamus of knockout mice. I concluded that Xrn1 is involved in regulation of energy expenditure and obesity.