A novel mechanism of myostatin regulation by its alternative splicing variant during myogenesis in avian species.
Myostatin (MSTN) is a key negative regulator of muscle growth and development, and an increase of muscle mass is achieved by inhibiting MSTN signaling. In the current study, five alternative splicing isoforms of MSTN mRNAs in avian species were identified in various tissues. Among these five, three truncated forms of myostatin, MSTN-B, -C, and -E created premature stop codons and produced partial MSTN prodomains encoded from exon 1. MSTN-B is the second dominant isoform following full-length MSTN-A, and their expression was dynamically regulated during muscle development of chicken, turkey, and quail in vivo and in vitro. To clarify the function of MSTN-B, two stable cell lines of quail myoblasts (QM7) were generated to overexpress MSTN-A or MSTN-B. Interestingly, MSTN-B promoted both cell proliferation and differentiation similar to the function of the MSTN prodomain to counteract the negative role of MSTN on myogenesis. The coimmunoprecipitation assay revealed that MSTN-B binds to MSTN-A and reduces the generation of mature MSTN. Furthermore, the current study demonstrated that the partial prodomain encoded from exon 1 is critical for binding of MSTN-B to MSTN-A. Altogether, these data imply that alternative splicing isoforms of MSTN could negatively regulate pro-myostatin processing in muscle cells and prevent MSTN-mediated inhibition of myogenesis in avian species.
Department of Animal Sciences, The Ohio State University, Columbus, Ohio; Department of Animal Biotechnology, Kyungpook National University, Sangju, Gyeongbuk, Republic of Korea; and.
Sangsu
S
Shin
Department of Animal Sciences, The Ohio State University, Columbus, Ohio;
Yan
Y
Song
Department of Animal Sciences, The Ohio State University, Columbus, Ohio; Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, Ohio.
Jinsoo
J
Ahn
Department of Animal Sciences, The Ohio State University, Columbus, Ohio;
Eunsoo
E
Kim
Department of Animal Sciences, The Ohio State University, Columbus, Ohio;
Paula
P
Chen
Department of Animal Sciences, The Ohio State University, Columbus, Ohio;
Shujin
S
Yang
Department of Animal Sciences, The Ohio State University, Columbus, Ohio;
Yeunsu
Y
Suh
Department of Animal Sciences, The Ohio State University, Columbus, Ohio; Interdisciplinary Ph.D. Program in Nutrition, The Ohio State University, Columbus, Ohio lee.2626@osu.edu.
Kichoon
K
Lee
D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D002645:Chickens / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D011784:Quail / Q000502:physiology*; D013045:Species Specificity; D014422:Turkeys / Q000502:physiology*
D055435:Myostatin; D020033:Protein Isoforms
alternative splicing; bird; muscle; myogenesis; myostatin