Background: Cellular homeostasis is regulated by the intricate interplay between a plethora of signaling pathways and “energetic sensors” in organs. In order to maintain energy balance, induction or repression of metabolic pathways must be regulated and act in concert with the energetic demands of the cell at a given point in time. A new class of small noncoding RNAs, the microRNAs (miRNAs), has added yet further complexity to the control of metabolic homeostasis. Objective: Understanding the damages induced by toxins in the liver and the intestine as well as the interplay between the miRNome and transcriptome first requires baseline characterization in these tissues in healthy animals under cellular homeostasis. Methods: The liver (main site for detoxification) and the gut (primary exposure routes for contaminant exposure) were dissected out (wildtype fish), total and small RNA extracted, mRNA and miRNA libraries constructed and subjected to high throughput sequencing. Differential Expression (DE) analysis was performed comparing liver with gut and an “miRNA matrix” that integrates the miRNA-seq and mRNA-seq data was constructed. Results: Both the miRNome and transcriptome of the liver and gut tissues were characterized and putative novel miRNAs were identified. Exploration of the “miRNA matrix” regulatory network revealed that miRNAs uniquely expressed in the liver or gut tissue regulated fundamental cellular processes important for both organs, and that commonly expressed miRNAs in both tissues regulated biological processes that were specific to either the liver or the gut. Conclusion: The result of our analyses revealed new insights into microRNA function in these tissues.

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MicroRNA 与目标基因在成年斑马鱼 (Danio rerio) 细胞稳态中的相互作用

背景：细胞稳态是由器官中大量信号通路和“能量传感器”之间复杂的相互作用调节的。为了维持能量平衡，代谢途径的诱导或抑制必须受到调节，并与细胞在给定时间点的能量需求相一致。一类新的小非编码 RNA，即 microRNA (miRNA)，进一步增加了代谢稳态控制的复杂性。目的：了解肝脏和肠道毒素引起的损害以及 miRNome 和转录组之间的相互作用，首先需要在细胞稳态下对健康动物的这些组织进行基线表征。方法：解剖肝脏（解毒的主要部位）和肠道（污染物暴露的主要暴露途径）（野生型鱼），提取总 RNA 和小 RNA，构建 mRNA 和 miRNA 文库并进行高通量测序。对肝脏和肠道进行差异表达（DE）分析，并构建了整合 miRNA-seq 和 mRNA-seq 数据的“miRNA 矩阵”。结果：肝脏和肠道组织的 miRNA 和转录组均得到了表征，并鉴定出了假定的新 miRNA。对“miRNA 矩阵”调控网络的探索表明，肝脏或肠道组织中独特表达的 miRNA 调节对这两个器官都很重要的基本细胞过程，而这两种组织中普遍表达的 miRNA 调节肝脏或肠道特有的生物过程。 。结论：我们的分析结果揭示了对这些组织中 microRNA 功能的新见解。