Wang Li-Chun, Hung Wan-Tzu, Pan Huichin, Chen Kuan-Yu, Wu Yi-Chun, Liu Yu-Fan, Hsiao Kuang-Ming
Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan, ROC.
Biochem Biophys Res Commun. 2008 Feb 15;366(3):705-9. doi: 10.1016/j.bbrc.2007.12.024. Epub 2007 Dec 17.
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.
类肌肉失明（MBNL）蛋白是组织特异性可变剪接调节因子。MBNL功能障碍与扩展的CUG重复序列相关的强直性肌营养不良（DM）的发病机制有关。在本研究中，我们描述了秀丽隐杆线虫肌肉失明（CeMbl）基因的鉴定和功能特征。CeMbl是一个单一基因，通过可变剪接产生两种异构体（CeMBL-A和CeMBL-B）。它在C3H1锌指结构域与人类MBNL1具有高度同源性。CeMbl转录本在幼虫和成虫阶段均可检测到。然而，通过RNA介导的干扰使CeMbl失活仅在成虫期导致肌肉表型。使用抗纽蛋白抗体进行的免疫荧光染色显示，受影响蠕虫的致密体组织被破坏。我们的结果证明了CeMbl对肌肉结构和功能的生长依赖性需求。它们还为扩展的CUG重复序列的发育调控毒性提供了可能的分子基础。
