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