In Ka, Hye Seo, Hyemin Choi, Youngsook Kim, Joohee Cho, Mina Choi, Seok-Yong Park, Sujeong Han, Sora An, Jinsu Chung, Hak Suk Yang, Young Kim, Min Jung 2024-01-19T15:02:56Z 2024-01-19T15:02:56Z 2021-09-05 2021-04 1741-7007 https://pubs.kist.re.kr/handle/201004/117199 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. English BMC Loss of splicing factor IK impairs normal skeletal muscle development Article 10.1186/s12915-021-00980-y 1 BMC BIOLOGY, v.19, no.1 BMC BIOLOGY 19 1 N scie scopus 000635651200001 2-s2.0-85103745869 Biology Life Sciences & Biomedicine - Other Topics Article IK Zebrafish CRISPR Cas9 Skeletal muscles Myogenesis