title: H19 Long Noncoding RNA Regulates Intestinal Epithelial Barrier Function via MicroRNA 675 by Interacting with RNA-Binding Protein HuR.
abstract: The disruption of the intestinal epithelial barrier function occurs commonly in various pathologies, but the exact mechanisms responsible are unclear. The H19 long noncoding RNA (lncRNA) regulates the expression of different genes and has been implicated in human genetic disorders and cancer. Here, we report that H19 plays an important role in controlling the intestinal epithelial barrier function by serving as a precursor for microRNA 675 (miR-675). H19 overexpression increased the cellular abundance of miR-675, which in turn destabilized and repressed the translation of mRNAs encoding tight junction protein ZO-1 and adherens junction E-cadherin, resulting in the dysfunction of the epithelial barrier. Increasing the level of the RNA-binding protein HuR in cells overexpressing H19 prevented the stimulation of miR-675 processing from H19, promoted ZO-1 and E-cadherin expression, and restored the epithelial barrier function to a nearly normal level. In contrast, the targeted deletion of HuR in intestinal epithelial cells enhanced miR-675 production in the mucosa and delayed the recovery of the gut barrier function after exposure to mesenteric ischemia/reperfusion. These results indicate that H19 interacts with HuR and regulates the intestinal epithelial barrier function via the H19-encoded miR-675 by altering ZO-1 and E-cadherin expression posttranscriptionally.
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Zou
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Suraj K
authors.initials: SK
authors.lastname: Jaladanki
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
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, Maryland, USA Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Jun-Yao
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Laboratory of Genetics, National Institute on Aging-IRP, NIH, Baltimore, Maryland, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA jwang@smail.umaryland.edu.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology*; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000235:genetics; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C000593997:Elavl1 protein, mouse; C094335:H19 long non-coding RNA; C548379:MIRN675 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein