Importance of non-canonical microRNAs in the mammalian brain

非典型 microRNA 在哺乳动物大脑中的重要性

• 批准号: RGPIN-2020-06364
• 负责人: Hébert, Sébastien
• 金额: $ 2.33万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=760662
• 关键词: Importance; non; canonical; microRNAs; mammalian

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.

在过去的十年中，神经科学研究界已经逐渐认识到小“微RNA”分子在大脑健康中的重要性。他们已经证明，micro-RNA是大脑功能的关键介质，通过控制蛋白质的数量，这些蛋白质对神经元的通讯、功能和衰老过程中的存活至关重要。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”micro-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，我们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典型micro-RNA在神经元健康中的贡献来回答这个问题。我们假设，非典型的小RNA，像他们的典型的对应物，是必要的，以确保神经元的功能和survival. Using我们在遗传学和分子生物学的专业知识，我们将开发新的小鼠模型，专门删除或插入选定的非典型的micro-RNAs直接在成年大脑的神经元。这种策略是在活体环境中研究这些分子的最佳策略，并且超过了文献中所有先前的研究。一旦完成，这些实验将为理解活体动物（包括人类）中的micro-RNA功能提供重要信息。这些研究结果、工具和生物模型也将为研究体内所有细胞类型中的所有类型的micro-RNA分子奠定基础。