title: Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by modulating the expression levels of tight junction proteins.
abstract: Epithelial cells line the intestinal mucosa and form an important barrier to a wide array of noxious substances in the lumen. Disruption of the barrier integrity occurs commonly in various pathologies. Long noncoding RNAs (lncRNAs) control diverse biological processes, but little is known about the role of lncRNAs in regulation of the gut permeability. Here we show that the lncRNA SPRY4-IT1 regulates the intestinal epithelial barrier function by altering expression of tight junction (TJ) proteins. SPRY4-IT1 silencing led to dysfunction of the epithelial barrier in cultured cells by decreasing the stability of mRNAs encoding TJ proteins claudin-1, claudin-3, occludin, and JAM-1 and repressing their translation. In contrast, increasing the levels of SPRY4-IT1 in the intestinal mucosa protected the gut barrier in mice exposed to septic stress by increasing the abundance of TJ proteins. SPRY4-IT1 directly interacted with TJ mRNAs, and this process was enhanced through the association with the RNA-binding protein HuR. Of interest, the intestinal mucosa from patients with increased gut permeability exhibited a decrease in the levels of SPRY4-IT1. These findings highlight a novel role for SPRY4-IT1 in controlling the intestinal epithelial barrier and define a mechanism by which SPRY4-IT1 modulates TJ expression by altering the stability and translation of TJ mRNAs.
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201 Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201 Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201.
authors.forename: Jaladanki N
authors.initials: JN
authors.lastname: Rao
authors.affiliation: Department of -Gastroenterology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Cao
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201 Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201.
authors.forename: Lan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201 Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201.
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Chung
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201 Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201 Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of -Gastroenterology, People's Hospital, Peking University, Beijing 100044, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, MD 21224.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201 Baltimore Veterans Affairs Medical Center, Baltimore, MD 21201 Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201 jwang@smail.umaryland.edu.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014176:Protein Biosynthesis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D062725:Tight Junction Proteins / Q000378:metabolism*
chemical_list: D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D062725:Tight Junction Proteins; C000605823:long noncoding RNA SPRY4-IT1, human