MicroRNA-26a/b and their host genes synergistically regulate triacylglycerol synthesis by targeting the INSIG1 gene

摘要

The microRNA-26 (miR-26) family is known to control adipogenesis in non-ruminants. Therngenomic loci of miR-26a and miR-26b have been localized in the introns of genes encodingrnfor the proteins of the carboxy-terminal domain RNA polymerase Ⅱpolypeptide A smallrnphosphatase (CTDSP) family. Insulin-induced gene 1 (INSIG1) encodes a protein with a keyrnrole in the regulation of lipogenesis in rodent liver. In the present study, we investigated thernsynergistic function of the miR-26 family and their host genes in goat mammary epithelialrncells (GMEC). Downregulation of miR-26a/b and their host genes in GMEC decreased thernexpression of genes relate to fatty acid synthesis (PPARG, LXRA, SREBF1, FASN, ACACA,rnGPAM, LPIN1, DGAT1 and SCD1), triacylglycerol accumulation and unsaturated fatty acidrnsynthesis. Luciferase reporter assays confirmed INSIG1 as a direct target of miR-26a/b.rnFurthermore, inhibition of the CTDSP family also downregulated the expression of INSIG1.rnTaken together, our findings highlight a functional association of miR-26a/b, their host genesrnand INSIG1, and provide new insights into the regulatory network controlling milk fatrnsynthesis in GMEC. The data indicate that targeting this network via nutrition might bernimportant for regulating milk fat synthesis in ruminants.