Exploration of RBM4-Regulated Splicing Events in Differentiating Adipocytes by Using Next-Generation Sequencing

Adipose tissue is a prominent organ that plays a pivotal role in regulating the nutrient and energy homeostasis. Two functionally distinct types of adipose tissue exist in mammals. White adipose tissue (WAT) efficiently reserves the triglyceride as energy source, whereas brown adipose tissue (BAT) is demonstrated to scatter the energy through thermogenesis and therefore counteract obesity in rodents. Even though, less is known about the presence and exact function of BAT in adult human particularly. Apart from the function, the knowledge of regulatory mechanism and factor which influences the development of BAT is sparse. RBM4 is demonstrated as the splicing factor to modulate the splicing of insulin receptor (IR) which largely contributes to the development of insulin-sensitive tissues, including skeletal muscle, pancreas and adipose tissue. The hyperlipidemia and reduced mass of brown adipose tissue of Rbm4-/- mice prompts the following investigation into the possible function of IR-mediated signaling on adipogenesis and metabolic homeostasis. The present result shows that the upregulated RBM4 induces the adipocyte-specific isoform of IR and PPAR which commits the complete development of C3H10T1/2 cells to the brown adipocytes-like lineage. These results have been accepted by BBA-Molecular Cell Research. The major purpose of this project is to reveal more adipogenesis-associated splicing event, especially the RBM4-specific target by using next generation sequencing (NGS) approach. The potential effect of RBM4 on the development of distinct type of adipocyte will be deciphered with the characterization of more RBM4-specific target. I anticipate the result of this project would bring a comprehensive scope on the post-transcriptional regulation of adipose differentiation. Moreover, the effect of RBM4a on the development and function of BAT may suggest its therapeutic potential for combating metabolic diseases and obesity.