microRNAs as determinants of metabolic phenotypes in teleost fish

硬骨鱼是最大的脊椎动物亚纲，已经进化到栖息于独特的生态位，并表现出各种各样的代谢表型。在整个生命周期和世代中，分子因素塑造了硬骨鱼的组织代谢表型。这项研究调查了一类特定的被称为microRNAs(MiRNAs)的分子在成年多骨鱼类及其发育和世代中塑造代谢表型的作用。MiRNAs是一种短的、非蛋白质编码的基因产物，它通过与靶向的mRNAs进行碱基互补配对来降低mRNA的稳定性并抑制其翻译。现在，它们被认为是哺乳动物新陈代谢的有力调节者，但它们在多骨鱼类中的相对作用尚不清楚。我们的研究将确定miRNAs在虹鳟鱼和斑马鱼这两个物种中的作用，这两个物种分别适合于确定miRNAs在成年多骨鱼类独特的代谢表型中的作用，以及跨发育和世代的作用。虹鲑鱼具有独特的代谢表型，它们耐受持续的禁食，对富含葡萄糖的饮食不耐受。自从最近彩虹鲑鱼基因组的发表以来，我们现在处理该物种中miRNAs的详细特征以及用于预测调控靶标的生物信息学工具。因此，我们将使用彩虹鲑鱼，一个成熟的代谢比较生理学模型，来确定miRNAs的调节和功能，包括物种特有的miRNAs，在其独特的代谢表型中。为了解决miRNAs在发育和世代中的代谢作用，我们将使用斑马鱼，这是一种世代时间较短的发育模型。我们将在基线条件下或在对额外代谢刺激的反应中，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。MiRNAs在这些时间尺度上出现代谢表型中的作用将通过确定miRNA在发育和配子中的差异表达以及通过调节已识别的miRNA候选的胚胎表达来确定。总之，这些方法将提供对miRNA分子在多骨鱼类生理代谢中的作用的比较深入的了解，这对水产养殖计划和营养以及加拿大环境中令人关注的鲤科和鲑鱼物种的生态毒理学具有重要意义。

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.