Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8302318 | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2014 | 10 Pages |
Abstract
Biosynthesis in vertebrates of long-chain polyunsaturated fatty acids (LC-PUFA) such as arachidonic (ARA; 20:4n â 6), eicosapentaenoic (EPA; 20:5n â 3) and docosahexaenoic (DHA; 22:6n â 3) acids requires the catalysis by fatty acyl desaturases (Fads). A vertebrate Fad with Î4 activity catalyzing the direct conversion of 22:5n â 3 to DHA was discovered in the marine teleost rabbitfish Siganus canaliculatus. Recent studies in vertebrates have shown that miRNAs may participate in the regulation of lipid metabolism at post-transcription level. However, their roles in LC-PUFA biosynthesis were not known. In the present study, in silico analysis predicts that the rabbitfish Î4 Fad may be a target of miR-17 and thus we cloned miR-17, which is located at the forepart of the miR-17-92 cluster. Dual luciferase reporter assays demonstrated that miR-17 targeted the 3â²UTR of Î4 Fad directly. Furthermore, the expression level of miR-17 displayed an inverse pattern with that of Î4 Fad mRNA in gill, liver and eyes, and also the Î4 Fad protein quantity in rabbitfish liver. Incubation of rabbitfish primary hepatocytes with linoleic acid (LA; 18:2n â 6), α-linolenic acid (LNA; 18:3n â 3), EPA or DHA showed differential effects on miR-17, Î4 Fad and Î6/Î5 Fad expression. LNA promoted the expression of miR-17 and Î6/Î5 Fad, but suppressed the expression of Î4 Fad. In contrast, LA and EPA decreased the expression of miR-17 and Î6/Î5 Fad, but had no effect on Î4 Fad. However, all the above were down-regulated by DHA. These data indicate that miR-17 was involved in the regulation of LC-PUFA biosynthesis in rabbitfish liver by targeting Î4 Fad.
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Authors
Qinghao Zhang, Dizhi Xie, Shuqi Wang, Cuihong You, Ãscar Monroig, Douglas R. Tocher, Yuanyou Li,