نبذة مختصرة : Recently, microRNAs (miRNAs) have emerged as crucial regulators of lipid metabolism. However, the miRNA-mediated regulatory mechanism on long-chain (≥C20) polyunsaturated fatty acids (LC-PUFA) biosynthesis in vertebrates remains largely unknown. Here, we address a potentially important role of miRNA-24 (miR-24) in the regulation of LC-PUFA biosynthesis in rabbitfish Siganus canaliculatus. miR-24 showed significantly higher abundance in liver of rabbitfish reared in brackish water than in seawater for fish fed vegetable oil diets and in S. canaliculatus hepatocyte line (SCHL) cells incubated with alpha-linolenic acid (ALA) than the control group. Similar expression patterns were also observed on the expression of sterol regulatory element-binding protein-1 (srebp1) and LC-PUFA biosynthesis related genes. While opposite results were observed on the expression of insulin-induced gene 1 (insig1), an endoplasmic reticulum membrane protein blocking Srebp1 proteolytic activation. Luciferase reporter assays revealed rabbitfish insig1 as a target of miR-24. Knockdown of miR-24 in SCHL cells resulted in increased Insig1 protein, and subsequently reduced mature Srebp1 protein and expression of genes required for LC-PUFA biosynthesis, and these effects could be attenuated after additional insig1 knockdown. Opposite results were observed with overexpression of miR-24. Moreover, increasing endogenous insig1 by knockdown of miR-24 inhibited Srebp1 processing and consequently suppressed LC-PUFA biosynthesis in rabbitfish hepatocytes. These results indicate a potentially critical role for miR-24 in regulating LC-PUFA biosynthesis through the Insig1/Srebp1 pathway by targeting insig1. This is the first report of miR-24 involved in LC-PUFA biosynthesis and thus may provide knowledge on the regulatory mechanisms of LC-PUFA biosynthesis in vertebrates.
Relation: Chen C, Wang S, Zhang M, Chen B, You C, Xie D, Liu Y, Monroig Ó, Tocher DR, Waiho K & Li Y (2019) miR-24 is involved in vertebrate LC-PUFA biosynthesis as demonstrated in marine teleost Siganus canaliculatus. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1864 (5), pp. 619-628. https://doi.org/10.1016/j.bbalip.2019.01.010; http://hdl.handle.net/1893/28658; WOS:000463123300002; 2-s2.0-85061112939; 1100693; http://dspace.stir.ac.uk/bitstream/1893/28658/1/2019-BBA-unformatted.pdf
Rights: This item has been embargoed for a period. During the embargo please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study. Accepted refereed manuscript of: Chen C, Wang S, Zhang M, Chen B, You C, Xie D, Liu Y, Monroig Ó, Tocher DR, Waiho K & Li Y (2019) miR-24 is involved in vertebrate LC-PUFA biosynthesis as demonstrated in marine teleost Siganus canaliculatus. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1864 (5), pp. 619-628. DOI: https://doi.org/10.1016/j.bbalip.2019.01.010 © 2019, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ ; http://creativecommons.org/licenses/by-nc-nd/4.0/ ; 2020-01-24 ; [2019-BBA-unformatted.pdf] Publisher requires embargo of 12 months after formal publication.
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