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RNA splicing regulated by USP15 is involved in neuromuscular functions

  • P1-324
  • 金 ゼヒョン / Jaehyun Kim:1 鶴田 文憲 / Fuminori Tsuruta:1 千葉 智樹 / Tomoki Chiba:1 
  • 1:筑波大院 生命環境科学 / Grad Sch of Life and Env Sci, Univ of Tsukuba, Tsukuba, Japan 

Alternative pre-mRNA splicing plays an important role in generating a huge number of proteins from the limited number of genes. This process contributes to an expanding the protein functions in all of cells, including neurons and muscle cells. Given that disruption of mRNA splicing lead to neurodegenerative disorders such as amyotrophic lateral sclerosis and spinal muscular atrophy, RNA splicing might be fundamental for the regulation of neuromuscular functions. However, the molecular mechanism of how the failure in RNA splicing results in neuromuscular disorder is yet to be elucidated.
In this study, we found that deubiquitinating enzyme, ubiquitin specific peptidase 15 (USP15), is associated with RNA splicing that underlies the control of neuromuscular functions. USP15 deficient mice exhibited ataxia-like behaviors resulting from the morphological defect of cerebellum and skeletal muscle. We also found that USP15 interacts with several factors, which play key roles in RNA splicing. Furthermore, multiple genes in USP15 deficient mice, which may be related to neuromuscular disorders, were widely changed in RNA splicing. Taken together, these data suggest that loss of USP15 may bring about aberrant gene expression mediated by misregulation of RNA splicing, and thereby impairs neuromuscular functions.

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