Transformer 2β homolog (Drosophila) (TRA2B) regulates protein kinase C δI (PKCδI) splice variant expression during 3T3L1 preadipocyte cell cycle.

Obesity is characterized by adipocyte hyperplasia and hypertrophy. We previously showed that expression is dysregulated in obesity (Carter, G., Apostolatos, A., Patel, R., Mathur, A., Cooper, D., Murr, M., and Patel, N. A. (2013) ISRN Obes. 2013, 161345). Using 3T3L1 preadipocytes, we studied adipogenesis in vitro and showed that expression of duanyu1531δ splice variants, and have different expression patterns during adipogenesis (Patel, R., Apostolatos, A., Carter, G., Ajmo, J., Gali, M., Cooper, D. R., You, M., Bisht, K. S., and Patel, N. A. (2013) J. Biol. Chem. 288, 26834-26846). Here, we evaluated the role of duanyu1531δI splice variant during adipogenesis. Our results indicate that duanyu1531δI expression level is high in preadipocytes and decreasing duanyu1531δI accelerated terminal differentiation. Our results indicate that duanyu1531δI is required for mitotic clonal expansion of preadipocytes. We next evaluated the splice factor regulating the expression of duanyu1531δI during 3T3L1 adipogenesis. Our results show TRA2B increased duanyu1531δI expression. To investigate the molecular mechanism, we cloned a heterologous splicing duanyu1531δ minigene and showed that inclusion of duanyu1531δ exon 9 is increased by TRA2B. Using mutagenesis and a RNA-immunoprecipitation assay, we evaluated the binding of Tra2β on duanyu1531δI exon 9 and show that its association is required for duanyu1531δI splicing. These results provide a better understanding of the role of duanyu1531δI in adipogenesis. Determination of this molecular mechanism of alternative splicing presents a novel therapeutic target in the management of obesity and its co-morbidities.

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