RBM3 enhances cold resistance by regulating thermogenic gene expressions

Abstract

Mammals are thermostatic animals and can regulate their body temperature within a precise range, irrespective of ambient temperature conditions. However, the mechanisms of how a body temperature is controlled in cold environments are still unclear. Here, we report that RNA binding motif protein 3 (RBM3) is crucial for maintaining body temperature in response to cold stimulation. RBM3, the RNA binding protein that stabilizes the target mRNA, is one of the significant proteins induced by cold stimulation. The Rbm3 knockout (Rbm3-/-) juvenile mice are sensitive to cold exposure and cannot maintain their body temperature. Notably,Rbm3-/-mice decreased the expression level of UCP1 and UCP3, pivotal for thermogenesis in brown adipose tissue (BAT) and skeletal muscle, respectively. We also found that a defect in RBM3 increases the size of lipid droplets in the BAT. Additionally, UCP1 expression is canceled by cold stimulation inRbm3-/-BAT. On the other hand, RBM3 deficiency has little effect on cold-induced UCP3 expression in skeletal muscle. These data suggest that RBM3 prevents body temperature reduction induced by cold stimulation via expressing UCP1 in BAT. Our findings provide a possibility that RBM3 is a crucial regulator of thermogenesis in juvenile mice with unstable body temperature regulation.