lncRNA H19 interacts with polypyrimidine tract-binding protein 1 to reprogram hepatic lipid homeostasis

ABSTRACT

H19 is an imprinted long non-coding RNA abundantly expressed in embryonic liver and repressed after birth. Here we show that H19 serves as a lipid sensor by synergizing with RNA-binding protein PTBP1 to modulate hepatic metabolic homeostasis. H19RNA interacts with PTBP1 to facilitate its association with SREBP1c mRNA and protein, leading to increased stability and nuclear transcriptional activity. H19 and PTBP1 are upregulated by fatty acids in hepatocytes and in diet-induced fatty liver, which further augments lipid accumulation. Ectopic expression of H19 induces steatosis and pushes the liver into a "pseudo fed" state in response to fasting by promoting SREBP1c protein cleavage and nuclear translocation. Deletion of H19 or knockdown of PTBP1 abolishes high-fat and high-sucrose (HFHS) diet-induced steatosis. Our study unveils a H19/PTBP1/SREBP1 feedforward amplifying signaling pathway to exacerbate the development of fatty liver. This article is protected by copyright. All rights reserved.

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