期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 409, 期 1, 页码 64-69出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2011.04.106
关键词
Actinin-associated LIM protein 3 (PDLIM3/ALP); Alternative splicing; MBNL; Myotonic dystrophy; Sarcoplasmic/endoplasmic reticulum Ca-ATPase 1 (SERCA1); ZASP-like motif
资金
- NCNP, Ministry of Health, Labor and Welfare, Japan [20B-13]
- Grants-in-Aid for Scientific Research [23700439] Funding Source: KAKEN
Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder of muscular dystrophy characterized by muscle weakness and wasting. DM1 is caused by expansion of CTG repeats in the 3'-untranslated region (3'-UTR) of DM protein kinase (DMPK) gene. Since CUG-repeat RNA transcribed from the expansion of CTG repeats traps RNA-binding proteins that regulate alternative splicing, several abnormalities of alternative splicing are detected in DM1, and the abnormal splicing of important genes results in the appearance of symptoms. In this study, we identify two abnormal splicing events for actinin-associated LIM protein 3 (PDLIM3/ALP) and fibronectin 1 (FN1) in the skeletal muscles of DM1 patients. From the analysis of the abnormal PDLIM3 splicing, we propose that ZASP-like motif-deficient PDLIM3 causes the muscular symptoms in DM. PDLIM3 binds alpha-actinin 2 in the Z-discs of muscle, and the ZASP-like motif is needed for this interaction. Moreover, in adult humans, PDLIM3 expression is highest in skeletal muscles, and PDLIM3 splicing in skeletal muscles is regulated during human development. (C) 2011 Elsevier Inc. All rights reserved.
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