Department of Biomedical Sciences, Chung Shan Medical University, Taichung, 402, Taiwan.
Cell Mol Life Sci. 2011 Apr;68(7):1255-67. doi: 10.1007/s00018-010-0522-4. Epub 2010 Sep 17.
We have utilized Caenorhabditis elegans as a model to investigate the toxicity and underlying mechanism of untranslated CAG repeats in comparison to CUG repeats. Our results indicate that CAG repeats can be toxic at the RNA level in a length-dependent manner, similar to that of CUG repeats. Both CAG and CUG repeats of toxic length form nuclear foci and co-localize with C. elegans muscleblind (CeMBL), implying that CeMBL may play a role in repeat RNA toxicity. Consistently, the phenotypes of worms expressing toxic CAG and CUG repeats, including shortened life span and reduced motility rate, were partially reversed by CeMbl over-expression. These results provide the first experimental evidence to show that the RNA toxicity induced by expanded CAG and CUG repeats can be mediated, at least in part, through the functional alteration of muscleblind in worms.
我们利用秀丽隐杆线虫作为模型，研究了未翻译的 CAG 重复与 CUG 重复的毒性和潜在机制。我们的结果表明，CAG 重复在 RNA 水平上具有长度依赖性毒性，与 CUG 重复相似。具有毒性长度的 CAG 和 CUG 重复均形成核斑点，并与秀丽隐杆线虫肌肉萎缩蛋白（CeMBL）共定位，这表明 CeMBL 可能在重复 RNA 毒性中发挥作用。一致地，表达毒性 CAG 和 CUG 重复的蠕虫表型，包括寿命缩短和运动速度降低，部分通过 CeMbl 过表达得到逆转。这些结果提供了第一个实验证据，表明扩展的 CAG 和 CUG 重复引起的 RNA 毒性至少部分可以通过肌肉萎缩蛋白在蠕虫中的功能改变来介导。
