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miR-33 基因在海洋硬骨鱼类中被鉴定出来:在调控 Siganus canaliculatus 中 LC-PUFA 生物合成中的潜在作用。

The miR-33 gene is identified in a marine teleost: a potential role in regulation of LC-PUFA biosynthesis in Siganus canaliculatus.

机构信息

Marine Biology Institute &Guangdong Provincial Key Laboratory of Marine Biotechnology, Shantou University, Shantou, Guangdong, China.

Institute of Aquaculture, Faculty of Natural Sciences, University of Stirling, Stirling, Scotland, UK.

出版信息

Sci Rep. 2016 Sep 19;6:32909. doi: 10.1038/srep32909.

Abstract

As the first marine teleost demonstrated to have the ability to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFA) from C18 PUFA precursors, rabbitfish Siganus canaliculatus provides a good model for studying the regulatory mechanisms of LC-PUFA biosynthesis in teleosts. Here the potential roles of miR-33 in such regulation were investigated. The miR-33 gene was identified within intron 16 of the gene encoding sterol regulatory element-binding protein 1 (Srebp1), an activator of LC-PUFA biosynthesis. Expression of miR-33 in rabbitfish tissues correlated with that of srebp1, while its expression in liver was highly responsive to ambient salinities and PUFA components, factors affecting LC-PUFA biosynthesis. Srebp1 activation promoted the expression of Δ4 and Δ6 Δ5 fatty acyl desaturases (Fad), key enzymes for LC-PUFA biosynthesis, accompanied by elevated miR-33 abundance in rabbitfish hepatocytes. miR-33 overexpression induced the expression of the two fad, but suppressed that of insulin-induced gene 1 (insig1), which encodes a repressor blocking Srebp proteolytic activation and has targeting sites of miR-33. These results indicated that miR-33, cooperating with Srebp1, may be involved in regulation of LC-PUFA biosynthesis by facilitating fad expression, probably through targeting insig1. To our knowledge, this is the first report of the participation of miR-33 in LC-PUFA biosynthesis in vertebrates.

摘要

作为第一个被证明具有从 C18PUFA 前体生物合成长链多不饱和脂肪酸(LC-PUFA)能力的海洋硬骨鱼类,兔鱼 Siganus canaliculatus 为研究硬骨鱼类 LC-PUFA 生物合成的调控机制提供了一个很好的模型。本研究探讨了 miR-33 在这种调控中的潜在作用。miR-33 基因位于编码固醇调节元件结合蛋白 1(Srebp1)的基因的内含子 16 内,Srebp1 是 LC-PUFA 生物合成的激活剂。兔鱼组织中 miR-33 的表达与 srebp1 的表达相关,而其在肝脏中的表达对环境盐度和 PUFA 成分(影响 LC-PUFA 生物合成的因素)高度敏感。Srebp1 激活促进了 Δ4 和 Δ6 Δ5 脂肪酸去饱和酶(Fad)的表达,这是 LC-PUFA 生物合成的关键酶,伴随着兔鱼肝细胞中 miR-33 丰度的升高。miR-33 过表达诱导了这两个 fad 的表达,但抑制了胰岛素诱导基因 1(insig1)的表达,后者编码一种阻止 Srebp 蛋白水解激活的抑制剂,并且有 miR-33 的靶向位点。这些结果表明,miR-33 与 Srebp1 合作,可能通过促进 fad 的表达参与 LC-PUFA 生物合成的调控,可能是通过靶向 insig1。据我们所知,这是 miR-33 参与脊椎动物 LC-PUFA 生物合成的首次报道。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0862/5027541/9b7957fdb74f/srep32909-f1.jpg

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