Precise regulation of RNA metabolism is crucial for dynamic gene expression and controlling cellular functions. In the nervous system, defects in RNA metabolism are implicated in disturbing brain homeostasis and development. Here we report that deubiquitinating enzyme, ubiquitin specific peptidase 15 (USP15), deubiquitinates terminal uridylyl transferase 1 (TUT1) and changes global RNA metabolism. We found that the expression of USP15 redistributes TUT1 from nucleolus to nucleoplasm, resulting in the stabilization of U6-snRNA. We also found that lack of the Usp15 gene induces impairment in motor ability with the unconventional cerebellar formation. Moreover, inhibition of the USP15-TUT1 cascade triggered mild and chronic endoplasmic reticulum (ER) stress. Therefore, our results suggest that USP15 is crucial for mRNA metabolism and maintains a healthy brain. These findings provide a possibility that disturbance of the USP15-TUT1 cascade may induce chronic and mild ER stress, leading to an acceleration of neurodegenerative phenotype.

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.