title: Posttranscriptional regulation of 14-3-3ζ by RNA-binding protein HuR modulating intestinal epithelial restitution after wounding.
abstract: The 14-3-3ζ is a member of the family of 14-3-3 proteins and participates in many aspects of cellular processes, but its regulation and involvement in gut mucosal homeostasis remain unknown. Here, we report that 14-3-3ζ expression is tightly regulated at the posttranscription level by RNA-binding protein HuR and plays an important role in early intestinal epithelial restitution after wounding. The 14-3-3ζ was highly expressed in the mucosa of gastrointestinal tract and in cultured intestinal epithelial cells (IECs). The 3' untranslated region (UTR) of the 14-3-3ζ mRNA was bound to HuR, and this association enhanced 14-3-3ζ translation without effect on its mRNA content. Conditional target deletion of HuR in IECs decreased the level of 14-3-3ζ protein in the intestinal mucosa. Silencing 14-3-3ζ by transfection with specific siRNA targeting the 14-3-3ζ mRNA suppressed intestinal epithelial restitution as indicated by a decrease in IEC migration after wounding, whereas ectopic overexpression of the wild-type 14-3-3ζ promoted cell migration. These results indicate that HuR induces 14-3-3ζ translation via interaction with its 3' UTR and that 14-3-3ζ is necessary for stimulation of IEC migration after wounding.
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Natasha Z
authors.initials: NZ
authors.lastname: Hansraj
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
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.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Turner
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland Baltimore Veterans Affairs Medical Center, Baltimore, Maryland Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland Baltimore Veterans Affairs Medical Center, Baltimore, Maryland rjaladanki@smail.umaryland.edu.
authors.forename: Jaladanki N
authors.initials: JN
authors.lastname: Rao
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D018938:Caco-2 Cells; D002465:Cell Movement; D000067780:ELAV-Like Protein 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D062326:Re-Epithelialization; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D000099221:Protein Kinase C zeta
chemical_list: D048948:14-3-3 Proteins; D020413:3' Untranslated Regions; D000067780:ELAV-Like Protein 1; D018832:Molecular Chaperones; D012333:RNA, Messenger; C000590975:Ywhaz protein, mouse; C098770:ELAVL1 protein, human; C000593997:Elavl1 protein, mouse; C000593998:Elavl1 protein, rat; C490392:Prkcz protein, rat; D000099221:Protein Kinase C zeta; C572235:YWHAZ protein, human
keywords: Epithelial cell migration; mucosal injury; posttranscriptional regulation; rapid epithelial repair