title: A long non-coding RNA, APOA4-AS, regulates APOA4 expression depending on HuR in mice.
abstract: Long non-coding RNAs (lncRNAs) have been shown to be critical biomarkers or therapeutic targets for human diseases. However, only a small number of lncRNAs were screened and characterized. Here, we identified 15 lncRNAs, which are associated with fatty liver disease. Among them, APOA4-AS is shown to be a concordant regulator of Apolipoprotein A-IV (APOA4) expression. APOA4-AS has a similar expression pattern with APOA4 gene. The expressions of APOA4-AS and APOA4 are both abnormally elevated in the liver of ob/ob mice and patients with fatty liver disease. Knockdown of APOA4-AS reduces APOA4 expression both in vitro and in vivo and leads to decreased levels of plasma triglyceride and total cholesterol in ob/ob mice. Mechanistically, APOA4-AS directly interacts with mRNA stabilizing protein HuR and stabilizes APOA4 mRNA. Deletion of HuR dramatically reduces both APOA4-AS and APOA4 transcripts. This study uncovers an anti-sense lncRNA (APOA4-AS), which is co-expressed with APOA4, and concordantly and specifically regulates APOA4 expression both in vitro and in vivo with the involvement of HuR.
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Wangshu
authors.initials: W
authors.lastname: Qin
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xinzhi
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Gastroenterology and Hepatology, Digestive Disease Institute, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xin Cun Road, Shanghai 200065, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Xie
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Jianan
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Linna
authors.initials: L
authors.lastname: Jia
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Dong
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: China and Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai 200444, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Yifa
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Life Sciences, Northeast Normal University, Changchun, Jilin 130024, China chenz100@nenu.edu.cn.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000096:biosynthesis / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D000067780:ELAV-Like Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D005234:Fatty Liver / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D014280:Triglycerides / Q000097:blood
chemical_list: D001054:Apolipoproteins A; D000067780:ELAV-Like Protein 1; C000593997:Elavl1 protein, mouse; D062085:RNA, Long Noncoding; D014280:Triglycerides; C022205:apolipoprotein A-IV; D002784:Cholesterol