Long noncoding RNA H19 interacts with polypyrimidine tract-binding protein 1 to reprogram hepatic lipid homeostasis.
Hepatology
; 67(5): 1768-1783, 2018 05.
Article
in En
| MEDLINE
| ID: mdl-29140550
ABSTRACT
H19 is an imprinted long noncoding RNA abundantly expressed in embryonic liver and repressed after birth. We show that H19 serves as a lipid sensor by synergizing with the RNA-binding polypyrimidine tract-binding protein 1 (PTBP1) to modulate hepatic metabolic homeostasis. H19 RNA interacts with PTBP1 to facilitate its association with sterol regulatory element-binding protein 1c mRNA and protein, leading to increased stability and nuclear transcriptional activity. H19 and PTBP1 are up-regulated 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 sterol regulatory element-binding protein 1c protein cleavage and nuclear translocation. Deletion of H19 or knockdown of PTBP1 abolishes high-fat and high-sucrose diet-induced steatosis. CONCLUSION:
Our study unveils an H19/PTBP1/sterol regulatory element-binding protein 1 feedforward amplifying signaling pathway to exacerbate the development of fatty liver. (Hepatology 2018;671768-1783).
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polypyrimidine Tract-Binding Protein
/
Heterogeneous-Nuclear Ribonucleoproteins
/
Lipogenesis
/
Fatty Liver
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RNA, Long Noncoding
Limits:
Animals
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Hepatology
Year:
2018
Type:
Article