title: Muscleblind participates in RNA toxicity of expanded CAG and CUG repeats in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, Chung Shan Medical University, Taichung, 402, Taiwan.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Wang
authors.forename: Kuan-Yu
authors.initials: KY
authors.lastname: Chen
authors.forename: Huichin
authors.initials: H
authors.lastname: Pan
authors.forename: Chia-Chieh
authors.initials: CC
authors.lastname: Wu
authors.forename: Po-Hsuan
authors.initials: PH
authors.lastname: Chen
authors.forename: Yuan-Ting
authors.initials: YT
authors.lastname: Liao
authors.forename: Chin
authors.initials: C
authors.lastname: Li
authors.forename: Min-Lang
authors.initials: ML
authors.lastname: Huang
authors.forename: Kuang-Ming
authors.initials: KM
authors.lastname: Hsiao
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010641:Phenotype; D012313:RNA / Q000235:genetics* / Q000633:toxicity*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D019680:Trinucleotide Repeat Expansion
chemical_list: D029742:Caenorhabditis elegans Proteins; D016601:RNA-Binding Proteins; C526262:mbl-1 protein, C elegans; D012313:RNA