title: Post-Transcriptional Regulation of Toll-Interacting Protein in the Intestinal Epithelium.
abstract: Immune responses against gut microbiota should be minimized to avoid unnecessary inflammation at mucosal surface. In this study, we analyzed the expression patterns of Toll-interacting protein (Tollip), an inhibitor of TLRs and IL-1 family cytokine-related intracellular signaling, in intestinal epithelial cells (IECs). Comparable mRNA expression was observed in murine small and large IECs (S-IECs and L-IECs). However, Tollip protein was only detected in L-IECs, but not in S-IECs. Similar results were obtained in germ-free mice, indicating that L-IEC-specific TOLLIP expression does not depend on bacterial colonization. Next, to understand the mechanisms underlying the post-transcriptional repression of Tollip, 3´-UTR-mediated translational regulation was evaluated. The region +1876/+2398 was responsible for the repression of Tollip expression. This region included the target sequence of miR-31. The inhibition of miR-31 restored the 3´-UTR-meditaed translational repression. In addition, miR-31 expression was significantly higher in S-IECs than in L-IECs, suggesting that miR-31 represses the translation of Tollip mRNA in S-IECs. Collectively, we conclude that the translation of Tollip is inhibited in S-IECs, at least in part, by miR-31 to yield L-IEC-specific high-level expression of the Tollip protein, which may contribute to the maintenance of intestinal homeostasis.
authors.affiliation: Department of Food Biochemistry and Biotechnology, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sugi
authors.affiliation: Department of Food Biochemistry and Biotechnology, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.|Department of Applied Biological Science, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Food Biochemistry and Biotechnology, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kurihara
authors.affiliation: Department of Food Biochemistry and Biotechnology, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.|Department of Applied Biological Science, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Department of Applied Biological Science, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Hikari
authors.initials: H
authors.lastname: Narabayashi
authors.affiliation: Department of Food Biochemistry and Biotechnology, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Hamamoto
authors.affiliation: Department of Food Biochemistry and Biotechnology, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Food Biochemistry and Biotechnology, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tsuda
authors.affiliation: Department of Applied Biological Science, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Shigemasa
authors.initials: S
authors.lastname: Hanazawa
authors.affiliation: Department of Food Biochemistry and Biotechnology, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hosono
authors.affiliation: Department of Food Biochemistry and Biotechnology, College of Bioresource Sciences, Nihon University, Kanagawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaminogawa
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D015152:Blotting, Northern; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D017930:Genes, Reporter; D007413:Intestinal Mucosa / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000070416:Antagomirs; D047908:Intracellular Signaling Peptides and Proteins; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C485837:Tollip protein, mouse