Muscleblind participates in RNA toxicity of expanded CAG and CUG repeats in Caenorhabditis elegans

作者：Wang Li Chun; Chen Kuan Yu; Pan Huichin; Wu Chia Chieh; Chen Po Hsuan; Liao Yuan Ting; Li Chin; Huang Min Lang; Hsiao Kuang Ming^*

来源：Cellular and Molecular Life Sciences, 2011, 68(7): 1255-1267.

DOI：10.1007/s00018-010-0522-4

• CAG and CUG repeats
• RNA toxicity
• C. elegans
• Muscleblind
• Sequestration

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.

• 出版日期2011-4