Loss of splicing factor IK impairs normal skeletal muscle development

BMC Biology

Hak Suk Chung¹  Jinsu An¹  Hye In Ka²  Young Yang²  Joohee Kim²  Min Jung Kim²  Mina Cho²  Sujeong Park²  Seok-Yong Choi³  Hyemin Seo⁴  Youngsook Choi⁵  Sora Han⁵ 

[1] Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST);Department of Biological Sciences, Sookmyung Women’s University;Department of Biomedical Sciences, Chonnam National University Medical School;Howard Hughes Medical Institute and Department of Molecular Biosciences, University of Texas at Austin;Research Institute of Women’s Health, Sookmyung Women’s University;

关键词: IK;    Zebrafish;    CRISPR/Cas9;    Skeletal muscles;    Myogenesis;   

DOI  :  10.1186/s12915-021-00980-y

来源: DOAJ

【 摘 要 】

Abstract Background IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo. Results The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells. Conclusion This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro.

【 授权许可】

Unknown