Satellite cells are muscle stem cells that are primarily quiescent in resting muscle. Upon injury, satellite cells will activate, proliferate, and differentiate to repair the damaged muscle. The quiescent state is a tightly regulated process. Dysregulation of the quiescent state will result in a depletion of the stem cell pool and impairment of muscle regeneration. Previously, our group has identified that the microRNA (miRNA) pathway is essential for the maintanence of satellite cell quiescence. As binding sites of miRNAs are on the 3’ UTR of mRNAs, the susceptibility of mRNA to miRNA regulation would depend on lengths of 3’ UTRs. Therefore, we hypothesized that alternative polyadenylation plays an important post-transcriptional regulation to maintain satellite cell quiescence....[ Read more ]

Satellite cells are muscle stem cells that are primarily quiescent in resting muscle. Upon injury, satellite cells will activate, proliferate, and differentiate to repair the damaged muscle. The quiescent state is a tightly regulated process. Dysregulation of the quiescent state will result in a depletion of the stem cell pool and impairment of muscle regeneration. Previously, our group has identified that the microRNA (miRNA) pathway is essential for the maintanence of satellite cell quiescence. As binding sites of miRNAs are on the 3’ UTR of mRNAs, the susceptibility of mRNA to miRNA regulation would depend on lengths of 3’ UTRs. Therefore, we hypothesized that alternative polyadenylation plays an important post-transcriptional regulation to maintain satellite cell quiescence. Alternative polyadenylation involves a number of proteins. In particular, poly(A) binding protein nuclear 1 (PABPN1) has been implicated as an important regulator of polyadenylation site selection. To better understand the role of PABPN1 in mRNA alternative polyadenylation, the expression level of PABPN1 in vivo in uninjured, regenerating and regenerated muscle was characterized. In addition, the expression level of PABPN1 during satellite cell activation on satellite cells associated muscle fibers ex vivo and during differentiation in primary myoblasts in vitro was investigated. We found that PABPN1 was highly expressed in regenerating muscle and activated satellite cells. Knockdown experiments were also performed on single fibers to investigate the effect of PABPN1 on satellite cell number and proliferation. The result of this project will shed lights on how alternative polyadenylation regulates muscle stem cell function.