Importance of non-canonical microRNAs in the mammalian brain

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In the past decade, the neuroscience research community has grown to appreciate the importance of the small "micro-RNA" molecules in brain health. They have shown that micro-RNAs are critical mediators of brain function by controlling the amount of proteins important for neuron communication, function, and survival during ageing. With the recent technological advancements in tools to analyse the genome, scientists have uncovered various classes of "atypical" micro-RNAs, collectively known as "non-canonical micro-RNAs". They are atypical because of their origin in the cell (specific regions within the DNA) and how they function to regulate proteins. Until now, it remains unclear if these are as important in neurons. We therefore answer this question by studying the contribution of four different classes of non-canonical micro-RNAs in neuron health. We hypothesize that non-canonical miRNAs, like their canonical counterparts, are necessary to assure neuron function and survival. Using our expertise in genetics and molecular biology, we will develop novel mouse models to specifically remove or insert selected non-canonical micro-RNAs in neurons directly in the adult brain. This strategy is optimal to study these molecules in a living context, and surpass all previous studies in the literature. Once completed, these experiments will provide important information for the understanding of micro-RNA functions in living animals, including in humans. These results, tools, and biological models developed in this research will also set the stage to study all classes of micro-RNA molecules in all cell types in the body.