Hammerhead-type Fxr Agonists Induce an Enhancer Rna Fincor That Ameliorates Nonalcoholic Steatohepatitis in Mice

Authors

Jinjing Chen
Ruoyu Wang
Feng Xiong
Hao Sun
Byron Kemper
Wenbo Li
Jongsook Kemper

Publication Date

4-15-2024

Journal

eLife

Abstract

The nuclear receptor, farnesoid X receptor (FXR/NR1H4), is increasingly recognized as a promising drug target for metabolic diseases, including nonalcoholic steatohepatitis (NASH). Protein-coding genes regulated by FXR are well known, but whether FXR also acts through regulation of long non-coding RNAs (lncRNAs), which vastly outnumber protein-coding genes, remains unknown. Utilizing RNA-seq and global run-on sequencing (GRO-seq) analyses in mouse liver, we found that FXR activation affects the expression of many RNA transcripts from chromatin regions bearing enhancer features. Among these we discovered a previously unannotated liver-enriched enhancer-derived lncRNA (eRNA), termed FXR-induced non-coding RNA (

Keywords

Animals, Mice, Enhancer RNAs, Non-alcoholic Fatty Liver Disease, RNA, Long Noncoding, Birds