| Title: |
MicroRNA-277 Modulates the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats. |
| Authors: |
Tan, Huiping1,2, Poidevin, Mickael1, He Li2, Chen, Dahua2 chendh@ioz.ac.cn, Jin, Peng1 peng.jin@emory.edu |
| Source: |
PLoS Genetics. May2012, Vol. 8 Issue 5, Special section p1-11. 11p. 2 Black and White Photographs, 2 Diagrams, 1 Chart, 3 Graphs. |
| Subject Terms: |
*MICRORNA, *ATAXIA, *FRAGILE X syndrome, *HUMAN chromosome abnormalities, *GENE expression |
| Abstract: |
Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder, has been recognized in older male fragile X premutation carriers and is uncoupled from fragile X syndrome. Using a Drosophila model of FXTAS, we previously showed that transcribed premutation repeats alone are sufficient to cause neurodegeneration. MiRNAs are sequence-specific regulators of post-transcriptional gene expression. To determine the role of miRNAs in rCGG repeat-mediated neurodegeneration, we profiled miRNA expression and identified selective miRNAs, including miR-277, that are altered specifically in Drosophila brains expressing rCGG repeats. We tested their genetic interactions with rCGG repeats and found that miR-277 can modulate rCGG repeat-mediated neurodegeneration. Furthermore, we identified Drep-2 and Vimar as functional targets of miR-277 that could modulate rCGG repeat-mediated neurodegeneration. Finally, we found that hnRNP A2/B1, an rCGG repeat-binding protein, can directly regulate the expression of miR-277. These results suggest that sequestration of specific rCGG repeat-binding proteins could lead to aberrant expression of selective miRNAs, which may modulate the pathogenesis of FXTAS by post-transcriptionally regulating the expression of specific mRNAs involved in FXTAS. [ABSTRACT FROM AUTHOR] |
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| Database: |
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