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Publication : Post-Transcriptional Regulation of Toll-Interacting Protein in the Intestinal Epithelium.

First Author  Sugi Y Year  2016
Journal  PLoS One Volume  11
Issue  10 Pages  e0164858
PubMed ID  27741296 Mgi Jnum  J:256804
Mgi Id  MGI:6099324 Doi  10.1371/journal.pone.0164858
Citation  Sugi Y, et al. (2016) Post-Transcriptional Regulation of Toll-Interacting Protein in the Intestinal Epithelium. PLoS One 11(10):e0164858
abstractText  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.
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