microRNAs as determinants of metabolic phenotypes in teleost fish

microRNA作为硬骨鱼代谢表型的决定因素

• 批准号: RGPIN-2017-05290
• 负责人: Mennigen, Jan
• 金额: $ 1.89万
• 依托单位: University of Ottawa
• 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=681570
• 关键词: microRNAs; determinants; metabolic; phenotypes; teleost

Bony fishes, the largest vertebrate infraclass, have evolved to inhabit unique ecological niches and exhibit a great variety of metabolic phenotypes. Molecular factors shape organismal metabolic phenotypes in bony fishes across the lifecycle and generations. This research investigates the role of a specific class of molecules called microRNAs (miRNAs) in shaping metabolic phenotypes in adult bony fishes and across their development and generations. miRNAs are short, non-protein coding gene products which decrease mRNA stability and inhibit their translation through complementary base pairing with targeted mRNAs. Now regarded as potent regulators of metabolism in mammals, their comparative role in bony fishes is poorly characterized. Our research will determine the role of miRNAs in two species, rainbow trout and zebrafish, which are well suited to determine the role of miRNAs in unique metabolic phenotypes in adult bony fishes and across development and generations, respectively. Rainbow trout possess a unique metabolic phenotype in that they tolerate sustained fasting and are intolerant to glucose-rich diets. Since the recent publication of the rainbow trout genome, we now dispose of a detailed characterization of miRNAs in this species and bioinformatics tools to predict regulated targets. We will thus use rainbow trout, a well-established model in the comparative physiology of metabolism, to determine regulation and function of miRNAs, including species-specific miRNAs, in its unique metabolic phenotype. To address metabolic roles of miRNAs across development and generations, we will use zebrafish, a developmental model with short generational time. We will determine the role of nutritional metabolic stimuli in early development on adult and trans-generational metabolic phenotypes under baseline conditions or in response to additional metabolic stimuli. The role of miRNAs in the emergence of metabolic phenotypes across these timescales will be determined by determining differential miRNA expression across development and in gametes, and by modulating embryonic expression of identified miRNA candidates. Together, these approaches will provide comparative insight into the role of miRNA molecules in the physiology metabolism in bony fish, which has important implication for aquaculture breeding programs and nutrition, as well as ecotoxicology of cyprinid and salmonid species of concern in the Canadian environment.

硬骨鱼类是最大的脊椎动物亚纲，已经进化到栖息在独特的生态位，并表现出多种代谢表型。分子因素在整个生命周期和世代中塑造硬骨鱼的有机代谢表型。本研究探讨了一类称为microRNAs （miRNAs）的特定分子在成年硬骨鱼及其发育和世代中形成代谢表型中的作用。mirna是短的非蛋白质编码基因产物，它通过与靶mRNA的互补碱基配对降低mRNA的稳定性并抑制mRNA的翻译。现在被认为是哺乳动物代谢的强有力的调节，它们在硬骨鱼类中的比较作用还不清楚。我们的研究将确定mirna在虹鳟鱼和斑马鱼两种物种中的作用，这两种物种非常适合分别确定mirna在成年硬骨鱼和跨发育和世代的独特代谢表型中的作用。虹鳟鱼具有独特的代谢表型，因为它们耐受持续禁食，不耐受富含葡萄糖的饮食。自从最近发表虹鳟鱼基因组以来，我们现在处理了该物种中mirna的详细表征和生物信息学工具来预测调节靶点。因此，我们将使用虹鳟鱼这一成熟的代谢生理学模型，来确定mirna的调节和功能，包括物种特异性mirna，在其独特的代谢表型中。为了解决mirna在发育和世代中的代谢作用，我们将使用斑马鱼，这是一种具有短世代时间的发育模型。我们将确定营养代谢刺激在成人和跨代代谢表型的早期发育中的作用，在基线条件下或在对额外代谢刺激的反应中。miRNA在这些时间尺度上代谢表型出现中的作用将通过确定发育和配子中的差异miRNA表达以及通过调节已鉴定的miRNA候选物的胚胎表达来确定。总之，这些方法将提供对miRNA分子在硬骨鱼生理代谢中的作用的比较见解，这对水产养殖育种计划和营养以及加拿大环境中关注的鲤科和鲑科物种的生态毒理学具有重要意义。