Importance of non-canonical microRNAs in the mammalian brain

在过去的十年里，神经科学研究界逐渐认识到小的“微rna”分子在大脑健康中的重要性。他们已经证明，在衰老过程中，微rna通过控制对神经元通讯、功能和存活至关重要的蛋白质的数量，是大脑功能的关键介质。随着基因组分析工具的最新技术进步，科学家们已经发现了各种类型的“非典型”微rna，统称为“非规范微rna”。它们是非典型的，因为它们起源于细胞（DNA内的特定区域），以及它们如何调节蛋白质。到目前为止，还不清楚这些在神经元中是否同样重要。因此，我们通过研究四种不同类型的非规范微rna在神经元健康中的作用来回答这个问题。我们假设非规范mirna，就像它们的规范对应物一样，是确保神经元功能和存活所必需的。利用我们在遗传学和分子生物学方面的专业知识，我们将开发新的小鼠模型，专门去除或直接在成人大脑的神经元中插入选择的非规范微rna。这种策略是在生活环境中研究这些分子的最佳策略，并且超越了文献中所有先前的研究。一旦完成，这些实验将为理解微rna在包括人类在内的活体动物中的功能提供重要信息。这些结果、工具和在本研究中开发的生物学模型也将为研究体内所有细胞类型中所有类别的微rna分子奠定基础。

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.