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miR-430a 通过靶向 teleost 中的 sqt 来调节左右不对称的发育。

miR-430a regulates the development of left-right asymmetry by targeting sqt in the teleost.

机构信息

MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.

MOE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.

出版信息

Gene. 2020 Jun 30;745:144628. doi: 10.1016/j.gene.2020.144628. Epub 2020 Mar 26.

DOI:10.1016/j.gene.2020.144628
PMID:32224271
Abstract

microRNAs (miRNAs) are short, endogenous non-coding RNAs that contain approximately 18-22 nucleotides. miRNAs are involved in gene regulation by recognizing and binding the 3'UTR of target gene. In our previous data, miR-430 family showed significant differential expression modes through metamorphosis in Japanese flounder. It was speculated that miR-430a plays a key role in left-right patterning. We predicted the targets of miR-430a and gene ontology (GO) was performed. We speculated miR-430a is involved in the basal molecular function and organ development. In Japanese flounder, sqt as a target of miR-430a was enriched into heart development term. Sqt has been reported to participate in mesendoderm formation and organ development. Cardiac morphogenesis is the first asymmetric development process, which breaks left-right symmetry in bilateria. It was used as a marker to detect L-R asymmetric effects of miR-430a. Overexpression and suppression of miR-430a resulted in abnormal KV (Kupffer's vesicles) development and disordered in nodal-related expression with consequent cardiac laterality. Squint mRNA of Japanese flounder (Posqt) as a target of miR-430a was overexpressed and caused similar phenotype with miR-430a suppression group, such as longer cilia in KV and high range of clmc2 and spaw ectopic expression. Moreover, rescue experiments were performed and suggested that cardiac and KV defections, induced by overexpressing miR-430a, could be rescued by injecting Posqt mRNA. These results suggested that miR-430a regulates the development of left-right asymmetry by targeting sqt in the teleost.

摘要

miRNAs(miRNAs)是短的、内源性的非编码 RNA,其包含约 18-22 个核苷酸。miRNAs 通过识别和结合靶基因的 3'UTR 参与基因调控。在我们之前的数据中,miR-430 家族在牙鲆变态过程中表现出明显的差异表达模式。推测 miR-430a 在左右模式形成中起关键作用。我们预测了 miR-430a 的靶基因,并进行了基因本体论(GO)分析。推测 miR-430a 参与了基础分子功能和器官发育。在牙鲆中,作为 miR-430a 靶标的 sqt 富集到心脏发育术语中。sqt 已被报道参与中胚层形成和器官发育。心脏形态发生是第一个不对称发育过程,它打破了两侧对称动物的左右对称性。它被用作检测 miR-430a 左右不对称效应的标志物。miR-430a 的过表达和抑制导致异常的 KV(Kupffer 小泡)发育和与节点相关的表达紊乱,从而导致心脏偏侧性。牙鲆的 Squint mRNA(Posqt)作为 miR-430a 的靶标被过表达,导致与 miR-430a 抑制组相似的表型,例如 KV 中的纤毛更长,clmc2 和 spaw 异位表达的范围更高。此外,进行了挽救实验,表明通过过表达 miR-430a 诱导的心脏和 KV 缺陷可以通过注射 Posqt mRNA 得到挽救。这些结果表明,miR-430a 通过靶向硬骨鱼类中的 sqt 来调节左右不对称的发育。

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