Loss of splicing factor IK impairs normal skeletal muscle development

Title
Loss of splicing factor IK impairs normal skeletal muscle development
Authors
정학숙안진수Hye In KaHyemin SeoYoungsook ChoiJoohee KimMina ChoSeok-Yong ChoiSujeong ParkSora HanYoung YangMin Jung Kim
Keywords
IK; Zebrafish; Crispr/Cas9; Skeletal muscles; Myogenesis
Issue Date
2021-04
Publisher
BMC BIOLOGY
Citation
VOL 19, 44
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.
URI
http://pubs.kist.re.kr/handle/201004/73009
ISSN
1741-7007
Appears in Collections:
KIST Publication > Article
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