Study of genetic modifiers of expanded CUG and CAG repeat RNA toxicity in C. elegans
碩士 === 國立中正大學 === 分子生物研究所 === 99 === Myotonic dystrophy (dystrophia myotonia, DM) is a dominant multisystemic disorder caused majorly by expanded CUG or CCUG repeat RNA through altering the function of RNA-binding proteins, including CUG-BP1and Muscleblind-like. Using Caenorhabditis elegans as a mod...
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ndltd-TW-098CCU000610012015-10-28T04:11:46Z http://ndltd.ncl.edu.tw/handle/96920428509555114601 Study of genetic modifiers of expanded CUG and CAG repeat RNA toxicity in C. elegans 探討線蟲之CUG 與CAG 重複序列RNA 毒性修飾基因 Wu, Chiachieh 伍佳傑 碩士 國立中正大學 分子生物研究所 99 Myotonic dystrophy (dystrophia myotonia, DM) is a dominant multisystemic disorder caused majorly by expanded CUG or CCUG repeat RNA through altering the function of RNA-binding proteins, including CUG-BP1and Muscleblind-like. Using Caenorhabditis elegans as a model, our laboratory has shown that expanded CUG as well as CAG repeat RNA may induce reversible toxicity and sequester C. elegans muscleblind (CeMBL) into nuclear foci. In this study, we further show that CeMBL overexpression may extend the shortened life span of CAG125 worms but can not rescue their reproduction capacity. These results confirm that CeMBL participates in repeat RNA pathogenesis. To investigate if there could be repeat RNA toxicity modifiers besides CeMBL, we then screen RNAi library using CUG83 worms. We have so far identified 4 potential genetic modifiers, including gcy-14, Fbxa-203, W05F2.4 and unc-89. Among them, gcy-14 and unc-89 knockdown significantly reduce CUG83 transgene expression and extend CUG83 worm life span. Fbxa-203 and W05F2.4 knockdown also extend CUG83 worm life span but does not reduce transgene expression. Although the underlying mechanism of regulating worm life span by these genes remains elusive, our results indicate that the CUG RNA toxicity can be suppressed by adjusting the expression level of specific genes. Hsiao, Kuangming 蕭光明 2011 學位論文 ; thesis 65 zh-TW |
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碩士 === 國立中正大學 === 分子生物研究所 === 99 === Myotonic dystrophy (dystrophia myotonia, DM) is a dominant multisystemic disorder caused majorly by expanded CUG or CCUG repeat RNA through altering the function of RNA-binding proteins, including CUG-BP1and Muscleblind-like. Using Caenorhabditis elegans as a model, our laboratory has shown that expanded CUG as well as CAG repeat RNA may induce reversible toxicity and sequester C. elegans muscleblind (CeMBL) into nuclear foci. In this study, we further show that CeMBL overexpression may extend the shortened life span of CAG125 worms but can not rescue their reproduction capacity. These results confirm that CeMBL participates in repeat RNA pathogenesis. To investigate if there could be repeat RNA toxicity modifiers besides CeMBL, we then screen RNAi library using CUG83 worms. We have so far identified 4 potential genetic modifiers, including gcy-14, Fbxa-203, W05F2.4 and unc-89. Among them, gcy-14 and unc-89 knockdown significantly reduce CUG83 transgene expression and extend CUG83 worm life span. Fbxa-203 and W05F2.4 knockdown also extend CUG83 worm life span but does not reduce transgene expression. Although the underlying mechanism of regulating worm life span by these genes remains elusive, our results indicate that the CUG RNA toxicity can be suppressed by adjusting the expression level of specific genes.
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author2 |
Hsiao, Kuangming |
author_facet |
Hsiao, Kuangming Wu, Chiachieh 伍佳傑 |
author |
Wu, Chiachieh 伍佳傑 |
spellingShingle |
Wu, Chiachieh 伍佳傑 Study of genetic modifiers of expanded CUG and CAG repeat RNA toxicity in C. elegans |
author_sort |
Wu, Chiachieh |
title |
Study of genetic modifiers of expanded CUG and CAG repeat RNA toxicity in C. elegans |
title_short |
Study of genetic modifiers of expanded CUG and CAG repeat RNA toxicity in C. elegans |
title_full |
Study of genetic modifiers of expanded CUG and CAG repeat RNA toxicity in C. elegans |
title_fullStr |
Study of genetic modifiers of expanded CUG and CAG repeat RNA toxicity in C. elegans |
title_full_unstemmed |
Study of genetic modifiers of expanded CUG and CAG repeat RNA toxicity in C. elegans |
title_sort |
study of genetic modifiers of expanded cug and cag repeat rna toxicity in c. elegans |
publishDate |
2011 |
url |
http://ndltd.ncl.edu.tw/handle/96920428509555114601 |
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