MicroRNAs Involved in the Regulation of LC-PUFA Biosynthesis in Teleosts: miR-33 Enhances LC-PUFA Biosynthesis in Siganus canaliculatus by Targeting insig1 which in Turn Upregulates srebp1

Sun, Jianhua; Zheng, Li Guo; Chen, Cui Ying; Zhang, Jin Ying; You, Cui Hong; Zhang, Qing Hao; Yu, Hong; Monroig, Óscar; Tocher, Douglas R.; Wang, Shu Qi; Li, Yuan You

doi:10.1007/s10126-019-09895-w

Cited by 18 publications

(19 citation statements)

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“…MiRNAs have emerged as key regulators of lipid metabolism in vertebrates (37), and, recently, we have demonstrated that miRNAs are also involved in the regulation of LC-PUFA biosynthesis in the marine teleost rabbitfish S. canaliculatus (23,24,35,36). However, the post-transcriptional regulatory mechanisms of miRNAs on LC-PUFA biosynthesis remain largely unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Multiple studies have established the important roles of certain miRNAs as key regulators of lipid metabolism in mammals (reviewed in 37). Our recent studies in rabbitfish Siganus canaliculatus also demonstrated that miR-17 and miR-146a regulate LC-PUFA biosynthesis by negative regulating the liver expression of Δ4 fads2 and elovl5, respectively (35)(36), while miR-24 and miR-33 can enhance LC-PUFA biosynthesis through activating the Srebp1 pathway by targeting insulin-induced gene protein 1 (Insig1) (23,24). These new data highlight the important roles of miRNAs in the regulation of LC-PUFA biosynthesis at a post-transcriptional level in vertebrates.…”

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confidence: 99%

“…FO-based) (18,19,22). Moreover, several transcriptional factors, including sterol regulatory element binding protein 1 (Srebp1) (23,24), nuclear factor Y (NF-Y) (25), hepatic nuclear factor 4 alpha (Hnf4α) (26,27), peroxisome proliferator-activated receptor gamma (Pparγ) (28) and stimulatory protein 1 (Sp1) (29), have been demonstrated to directly regulate the expression of fads and elovl genes at a transcriptional level. The liver X receptor (Lxr) is a member of the nuclear hormone receptor superfamily with important roles in the transcriptional control of lipid metabolism (30).…”

mentioning

confidence: 99%

“…Previous studies have shown that Lxr plays a critical role in regulation of LC-PUFA biosynthesis through direct regulation or Srebp1-dependent regulation of fads and elovl genes (32)(33)(34). Recently, we found that microRNAs (abbreviated as miRNAs or miR) also regulate the expression of fads and elovl genes in fish (23,24,35,36), suggesting that post-transcriptional regulation by miRNAs may be one of the key regulatory mechanisms of LC-PUFA biosynthesis. However, the mechanisms of the post-transcriptional regulation for LC-PUFA biosynthesis remained largely unclear in teleosts and other vertebrates.…”

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confidence: 99%

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miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα–Srebp1 pathway in the marine teleost Siganus canaliculatus

Chen

Wang

et al. 2020

Journal of Biological Chemistry

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MicroRNAs (miRNAs) have been recently shown to be important regulators of lipid metabolism. However, the mechanisms of miRNA-mediated regulation of long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis in vertebrates remain largely unknown. Herein, we for the first time addressed the role of miR-26a in LC-PUFA biosynthesis in the marine rabbitfish Siganus canaliculatus. The results showed that miR-26a was significantly down-regulated in liver of rabbitfish reared in seawater and in S. canaliculatus hepatocyte line (SCHL) incubated with the LC-PUFA precursor α-linolenic acid (ALA), suggesting that miR-26a may be involved in LC-PUFA biosynthesis due to its abundance being regulated by factors affecting LC-PUFA biosynthesis. Opposite patterns were observed in the expression of liver X receptor α (lxrα) and sterol regulatory element-binding protein-1 (srebp1), as well as the LC-PUFA biosynthesis related genes (Δ4 fads2, Δ6Δ5 fads2 and elovl5) in SCHL cells incubated with ALA. Luciferase reporter assays revealed rabbitfish lxrα as a target of miR-26a, and overexpression of miR-26a in SCHL cells markedly reduced protein levels of Lxrα, Srebp1 and Δ6Δ5 Fads2 induced by the agonist T0901317. Moreover, increasing endogenous Lxrα by knockdown of miR-26a facilitated Srebp1 activation and concomitant increased expression of genes involved in LC-PUFA biosynthesis, and consequently promoted LC-PUFA biosynthesis both in vitro and in vivo. These results indicate a critical role of miR-26a in regulating LC-PUFA biosynthesis through targeting the Lxrα-Srebp1 pathway and provide new insights into the regulatory network controlling LC-PUFA biosynthesis and accumulation in vertebrates.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα–Srebp1 pathway in the marine teleost Siganus canaliculatus

Chen

Wang

et al. 2020

Journal of Biological Chemistry

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“…The hepatocyte nuclear factor 4 (Hnf4α) another lipogenesis regulator, is recently shown to be an essential regulator of LC-PUFA biosynthesis in a marine herbivorous fish Siganus caniliculatus by positively regulating both Fads and Elovl (Li et al, 2018, Dong et al, 2018. Furthermore, post-transcriptional regulation of fads and elovl5 involving the enhancement of Srebp1 through microRNAs and an insulin-induced gene was also shown in the same species (Sun et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Sterol regulatory element binding protein and Sp1 is required for transcriptional activation of a freshwater carnivorous fish (Channa striata) elovl5 elongase

Goh¹,

Kuah

Chew³

et al. 2019

Preprint

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Long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis involves the activities of two groups of enzymes, the fatty acyl desaturases (Fads) and elongases of very long-chain fatty acid (Elovl). Fish are major source of beneficial n-3 LC-PUFA in human diet and there is a considerable interest to elucidate the mechanism and regulatory aspects of LC-PUFA biosynthesis in farmed fish species. The promoter of elovl5 elongase, which catalyze the rate limiting reaction of adding two carbons to the C18 PUFA have been previously described and characterized from several marine and diadromous teleost species. We report here the cloning and characterization of the elovl5 promoter from two freshwater fish species, the carnivorous snakehead fish (Channa striata) and zebrafish. Results show the importance of sterol regulatory element binding protein (Srebp) and the corresponding sterol responsive element (SRE) in the core regulatory region of both promoters. Mutagenesis luciferase and electrophoretic mobility shift assays confirm that SRE is indispensable for basal transcriptional activation in both species. In addition, several Sp1 binding sites located in close proximity with SRE were present in the snakehead promoter, with one having a potential synergy with SRE in regulating elovl5 expression. The core elovl5 promoter fragments of both species also directed in vivo expression in the yolk syncytial layer of developing zebrafish embryos. This study is the first functional promoter analysis of Elovl5 in freshwater teleost.

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Biosynthesis of Polyunsaturated Fatty Acids—‘Many Can, Some Can’t’

Steinberg

2022

Aquatic Animal Nutrition

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MicroRNAs Involved in the Regulation of LC-PUFA Biosynthesis in Teleosts: miR-33 Enhances LC-PUFA Biosynthesis in Siganus canaliculatus by Targeting insig1 which in Turn Upregulates srebp1

Abstract: MicroRNAs involved in the regulation of LC-PUFA biosynthesis in teleosts: miR-33 enhances LC-PUFA biosynthesis in Siganus canaliculatus by targeting insig1 which in turn up-regulates srebp1

Cited by 18 publications

References 50 publications

miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα–Srebp1 pathway in the marine teleost Siganus canaliculatus

miR-26a mediates LC-PUFA biosynthesis by targeting the Lxrα–Srebp1 pathway in the marine teleost Siganus canaliculatus

Sterol regulatory element binding protein and Sp1 is required for transcriptional activation of a freshwater carnivorous fish (Channa striata) elovl5 elongase

Biosynthesis of Polyunsaturated Fatty Acids—‘Many Can, Some Can’t’

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