Growth-dependent effect of muscleblind knockdown on Caenorhabditis elegans.
The muscleblind-like (MBNL) proteins are tissue-specific alternative splicing regulators. Dysfunction of MBNL has been implicated in the pathogenesis of expanded CUG repeats-associated myotonic dystrophy (DM). In this study, we describe the identification and functional characterization of a Caenorhabditis elegans muscleblind (CeMbl) gene. CeMbl is a single gene alternatively spliced to generate two isoforms (CeMBL-A and CeMBL-B). It displays a high homology with human MBNL1 in the C3H1 zinc finger domains. CeMbl transcripts are detected in larval and adult stages. However, inactivation of CeMbl by RNA-mediated interference results in muscle phenotype only at adulthood. Immunofluorescence staining using anti-vinculin antibody reveals that the organization of dense body is disrupted in affected worms. Our results demonstrate a growth-dependent requirement of CeMbl on muscle structure and function. They also provide a possible molecular basis for the developmentally regulated toxicity of expanded CUG repeats.
Wang
Li-Chun
LC
Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan, ROC.
Hung
Wan-Tzu
WT
Pan
Huichin
H
Chen
Kuan-Yu
KY
Wu
Yi-Chun
YC
Liu
Yu-Fan
YF
Hsiao
Kuang-Ming
KM
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D009024:Morphogenesis / Q000502:physiology*; D018482:Muscle, Skeletal / Q000196:embryology* / Q000254:growth & development*; D016601:RNA-Binding Proteins / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D016601:RNA-Binding Proteins; C526262:mbl-1 protein, C elegans