Ultraconserved Element Uc.372 Drives Hepatic Lipid Accumulation by Suppressing MiR-195/miR4668 Maturation

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Feb 11

PMID 29426937

Citations 44

Authors

Jun Guo

Weiwei Fang

Libo Sun

Yonggang Lu

Lin Dou

Xiuqing Huang

Weiqing Tang

Liqing Yu

Jian Li

Affiliations

Soon will be listed here.

Abstract

Ultraconserved (uc) RNAs, a class of long non-coding RNAs (lncRNAs), are conserved across humans, mice, and rats, but the physiological significance and pathological role of ucRNAs is largely unknown. Here we show that uc.372 is upregulated in the livers of db/db mice, HFD-fed mice, and NAFLD patients. Gain-of-function and loss-of-function studies indicate that uc.372 drives hepatic lipid accumulation in mice by promoting lipogenesis. We further demonstrate that uc.372 binds to pri-miR-195/pri-miR-4668 and suppresses maturation of miR-195/miR-4668 to regulate expression of genes related to lipid synthesis and uptake, including ACC, FAS, SCD1, and CD36. Finally, we identify that uc.372 is located downstream of the insulinoma-associated 2 (INSM2) gene that is transcriptionally activated by upstream transcription factor 1 (USF1). Our findings reveal a novel mechanism by which uc.372 drives hepatic steatosis through inhibition of miR-195/miR-4668 maturation to relieve miR-195/miR-4668-mediated suppression of functional target gene expression.

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