Muscle stem cell (MuSC), also called satellite cell, is maintained in a quiescent state in resting muscles. While activated upon muscle injury, satellite cell proliferates quickly then undergoes differentiation and fusion to form newly generated myofibers. Satellite cell activation is tightly controlled by transcriptional and post-transcriptional regulations. Cytoplasmic polyadenylation element binding protein 1 ( CPEB1) was first identified to regulate Xenopus oocyte maturation through cytoplasmic polyadenylation. Furthermore, nuclear CPEB1 regulates alternative 3'UTR formation of its targets many of which are cell cycle-related genes. We hypothesize CPEB1 functions to regulate satellite cell activation. Here, we found that CPEB1 was upregulated and translocated into nucleus i...[ Read more ]

Muscle stem cell (MuSC), also called satellite cell, is maintained in a quiescent state in resting muscles. While activated upon muscle injury, satellite cell proliferates quickly then undergoes differentiation and fusion to form newly generated myofibers. Satellite cell activation is tightly controlled by transcriptional and post-transcriptional regulations. Cytoplasmic polyadenylation element binding protein 1 ( CPEB1) was first identified to regulate Xenopus oocyte maturation through cytoplasmic polyadenylation. Furthermore, nuclear CPEB1 regulates alternative 3'UTR formation of its targets many of which are cell cycle-related genes. We hypothesize CPEB1 functions to regulate satellite cell activation. Here, we found that CPEB1 was upregulated and translocated into nucleus in activated satellite cells. Loss of function analysis showed that CPEB1 knockdown delayed MuSC activation. Furthermore, we demonstrated that CPEB1 was quickly phosphorylated during satellite cell activation. Aurora A, which phosphorylated CPEB1, was dramatically increased in activated satellite cell. In addition, the highly selective Aurora A inhibitor MK5108 affected activation negatively by inhibiting CPEB1 phosphorylation. On the contrary, MuSC can be activated via CPEB1 phosphorylation by Insulin pathway. We also demonstrated that most of CPEB1 was not colocalized with Dcpla and eIF3b indicating CPEB1 regulated translation not through p-body and stress granule. The FRAP experiments showed that CPEB1 can form dynamic granule suggesting that CPEB1 regulates translation efficiency through dynamic puncta. To specifically investigate the targets of CPEB1, we found that myogenic factor, Myf5 and Myod harbored CPEs in their 3'UTRs. Therefore, we suppose that CPEB1 maintains quiescence through repressing Myf5 or MyoD translation in quiescent satellite cell. Upon stimuli exit, insulin activates Aurora A then induces CPEB1 phosphorylation to kick start the translation of Myf5 mRNA or MyoD mRNA for MuSC activation. The phosphorylated CPEB1 is translocated into nucleus to regulate alternative 3'UTR formation, resulting in 3'UTR globally for increased protein output and to promote MuSC activation.