Functional analysis of a drosophila micro-RNA and experimental validation of Targets
Final Report Abstract
microRNAs are recently discovered class of molecules which regulates gene expression by influencing the production of proteins from messenger RNAs. microRNAs are conserved across various multi-cellular organisms, and hence form important biological factors, which might play roles during development of organisms and have also been implicated in various diseases including cancer. About 30% of mammalian genes are postulated to be microRNA regulatable and 5-10% of all animal genomes encodes for microRNAs. Inspite of these features the functions of most of the microRNAs are not well understood. The machinery which microRNAs recruit to regulate genes is conserved in different species. One of the microRNAs expressed in the widely used genetic model Drosophila melanogaster (fruit fly) miR-14 regulates lifespan, fat metabolism and apoptosis. In this study we show that miR-14 targets one of the key hormone signaling molecule, the Ecdysone receptor (EcR) crucial for insect development. Lack of this microRNA is responsible for the shortening of lifespan and also cause defects to metamorphosis. We also found that Ecdysone hormone in turn regulates miR-14 during specific developmental stages. miR-14 thus becomes a major player in the auto-regulatory machinery by which the hormone signaling regulates its receptor levels. This finding is novel and quite relevant to microRNA studies as similar mechanisms might be functional in other microRNA-target regulation.
Publications
- microRNA miR-14 acts to modulate a positive autoregulatory loop controlling steroid hormone signaling in Drosophila. Genes Dev. 2007 Sep 15;21(18):2277-82
Varghese, J. and Cohen S. M.
