Deciphering extracellular microRNA communication system

破译细胞外microRNA通讯系统

• 批准号: RGPIN-2015-06217
• 负责人: Belleannee, Clemence
• 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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=684220
• 关键词: Deciphering; extracellular; microRNA; communication; system

***Ribonucleic acids (RNAs) are present in all cells as intermediates between genes and proteins and as small non-coding RNAs. Among these latter, microRNAs (miRNAs) control target genes expression and regulate many functions such as cell proliferation, differentiation and death. Importantly, miRNAs are involved in intercellular communication after being transferred from one cell to another by extracellular vesicles (EVs). However, despite their important role in intercellular communication, this mechanism remains poorly understood. Our research program aims to unravel the complexity of extracellular miRNA (ex-miRNA) signaling in the epididymis, the organ of the male reproductive system responsible for sperm maturation. To achieve this goal, we will (i) explore the synthesis and secretion pathways of ex-miRNAs in EVs, (ii) identify the cellular players involved in the ex-miRNA/EVs signaling, and (iii) identify target genes and cellular functions controlled by ex-miRNAs in the epididymis. In collaboration with experts from different fields we will use imaging, molecular biology and in vivo approaches on different transgenic mouse models. Thus, we aim to address fundamental biological principles of ex-miRNAs secretion, transport and function, and to identify key molecular events governing reproductive biology and, by extension, species survival.

* 核糖核酸（RNA）作为基因和蛋白质之间的中间体以及作为小的非编码RNA存在于所有细胞中。其中，microRNAs（miRNAs）控制靶基因的表达，并调节细胞增殖、分化和死亡等多种功能。重要的是，miRNA在通过细胞外囊泡（EV）从一个细胞转移到另一个细胞后参与细胞间通讯。然而，尽管它们在细胞间通讯中发挥重要作用，但这种机制仍然知之甚少。我们的研究计划旨在揭示附睾细胞外miRNA（ex-miRNA）信号传导的复杂性，附睾是男性生殖系统中负责精子成熟的器官。为了实现这一目标，我们将（i）探索EV中ex-miRNA的合成和分泌途径，（ii）鉴定参与ex-miRNA/EV信号传导的细胞参与者，以及（iii）鉴定附睾中由ex-miRNA控制的靶基因和细胞功能。我们将与来自不同领域的专家合作，在不同的转基因小鼠模型上使用成像、分子生物学和体内方法。因此，我们的目标是解决基本的生物学原则的前-miRNA的分泌，运输和功能，并确定关键的分子事件，管理生殖生物学，并通过扩展，物种生存。