The myostatin-induced E3 ubiquitin ligase RNF13 negatively regulates the proliferation of chicken myoblasts.

The ubiquitin ligase RING finger protein 13 gene (RNF13) was first identified in a screen for genes whose expression is regulated by myostatin in chicken fetal myoblasts. In this study, we demonstrate that the RNF13 gene is broadly expressed in many chicken tissues. The expression of RNF13 gradually decreases during skeletal myogenesis, and myostatin up-regulates RNF13 expression at both the transcriptional and translational levels. Interestingly, ectopic expression of RNF13 inhibits cell proliferation and suppresses the expression of the myogenic genes MyoD and Caveolin-3 in muscle cells. Moreover, recently, we have reported that RNF13 is a RING-type E3 ubiquitin ligase. In this report, we provide experimental evidence to show that mutations disrupting the RING finger abolish the growth-suppressive activity of RNF13, indicating that its E3 ligase activity is required for the inhibition of cell proliferation. Taken together, our findings show that RNF13 functions as an E3 ubiquitin ligase to negatively regulate cell proliferation.