HuR promotes triglyceride synthesis and intestinal fat absorption

Triacylglyceride (TAG) synthesis in the small intestine determines the absorption of dietary fat, but the mechanisms underlying are largely unknown. Here, we report that the RNA-binding protein HuR (ELAVL1) promotes TAG synthesis in the small intestine. HuR associates with the 3'UTR of Dgat2 mRNA and the introns 1 of Mgat2 pre-mRNA. Association of HuR with Dgat2 3'UTR stabilizes Dgat2 mRNA, while association of HuR with intron 1 of Mgat2 pre-mRNA promotes the processing of Mgat2 pre-mRNA. Intestinal epithelium-specific HuR knockout reduces the expression of DGAT2 and MGAT2, thereby reducing the dietary fat absorption through TAG synthesis and mitigating high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and obesity. Our findings highlight a critical role of HuR in promoting dietary fat absorption. Overall design: To investigate HuR binding mRNAs in intestinal fat absorption, we used mouse colon cancer cells CT26. WT for ribonucleoprotein immunoprecipitation assay using anti-endogenous HuR antibody. One input RNA(divided in three), and 3v3 co-immunoprecipitated RNA(IgG and HuR)respectively were used for next-generation sequencing