Thesis Title: miRNAs in the fly nervous system: insights into miR-285-regulated aging via the superoxide metabolism pathway
Post-transcriptional gene regulation by miRNAs provides an important and additional layer of regulatory complexity in neuronal networks. This thesis work explores the role of one Drosophila miRNA, miR-285, in the post-developmental brain, using miR-285 loss of function mutants. Interestingly, miR-285 acts to ‘promote’ age-related impairment in the male nervous system. Mutants lacking miR-285 are protected from age-progressive behavioral decline and live longer. miR-285 targets genes at multiple steps in the pathway for extracellular superoxide metabolism. Mutants show elevated superoxide flux, elevated ROS signaling and are protected against oxidative stress. Interestingly, miR-285 is expressed in glia at higher levels in young males than in older males. Young mutant males show reduced reproductive success. Thus, regulation of superoxide metabolism in the nervous system appears to be required for reproductive fitness, at the cost of accelerated aging in male Drosophila.
Figure legend: miR-285 (red) co-localizes largely with repo (green), a marker for glial cells in the Drosophila centralbrain.
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