The Conserved microRNA MiR-8 Tunes Atrophin Levels to Prevent Neurodegeneration in Drosophila

摘要: microRNAs (miRNAs) bind to specific messenger RNA targets posttranscriptionally modulate their expression. Understanding the regulatory relationships between miRNAs and remains a major challenge. Many reduce expression of inconsequential levels. It has also been proposed that might adjust target an optimal level. Here we analyze consequences mutating conserved miRNA miR-8 in Drosophila. We identify atrophin as direct miR-8. mutant phenotypes are attributable elevated activity, resulting apoptosis brain behavioral defects. Reduction levels miR-8-expressing cells below level generated by regulation is detrimental, providing evidence for "tuning target" relationship them. Drosophila related family mammalian transcriptional regulators, implicated neurodegenerative disorder DRPLA. The orthologs mammals.