CUGBP1 and HuR regulate E-cadherin translation by altering recruitment of E-cadherin mRNA to processing bodies and modulate epithelial barrier function.
The effectiveness and stability of epithelial barrier depend on apical junctional complexes, which consist of tight junctions (TJs) and adherens junctions (AJs). E-cadherin is the primary component of AJs, and it is essential for maintenance of cell-to-cell interactions and regulates the epithelial barrier. However, the exact mechanism underlying E-cadherin expression, particularly at the posttranscriptional level, remains largely unknown. RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HU antigen R (HuR) are highly expressed in the intestinal epithelial tissues and modulate the stability and translation of target mRNAs. Here, we present evidence that CUGBP1 and HuR interact directly with the 3'-untranslated region of E-cadherin mRNA and regulate E-cadherin translation. CUGBP1 overexpression in Caco-2 cells inhibited E-cadherin translation by increasing the recruitment of E-cadherin mRNA to processing bodies (PBs), thus resulting in an increase in paracellular permeability. Overexpression of HuR exhibited an opposite effect on E-cadherin expression by preventing the translocation of E-cadherin mRNA to PBs and therefore prevented CUGBP1-induced repression of E-cadherin expression. Elevation of HuR also abolished the CUGBP1-induced epithelial barrier dysfunction. These findings indicate that CUGBP1 and HuR negate each other's effects in regulating E-cadherin translation by altering the recruitment of E-cadherin mRNA to PBs and play an important role in the regulation of intestinal barrier integrity under various pathophysiological conditions.
Xin Hua Hospital Affiliated to School of Medicine, Shanghai JiaoTong University, Shanghai, China; and Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai, China yutingxi@hotmail.com.
Ting-Xi
TX
Yu
Xin Hua Hospital Affiliated to School of Medicine, Shanghai JiaoTong University, Shanghai, China; and Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai, China.
Bei-Lin
BL
Gu
Xin Hua Hospital Affiliated to School of Medicine, Shanghai JiaoTong University, Shanghai, China; and Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai, China.
Jun-Kai
JK
Yan
Xin Hua Hospital Affiliated to School of Medicine, Shanghai JiaoTong University, Shanghai, China; and Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai, China.
Jie
J
Zhu
Xin Hua Hospital Affiliated to School of Medicine, Shanghai JiaoTong University, Shanghai, China; and Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai, China.
Wei-Hui
WH
Yan
Xin Hua Hospital Affiliated to School of Medicine, Shanghai JiaoTong University, Shanghai, China; and.
Jie
J
Chen
Xin Hua Hospital Affiliated to School of Medicine, Shanghai JiaoTong University, Shanghai, China; and Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai, China.
Lin-Xi
LX
Qian
Xin Hua Hospital Affiliated to School of Medicine, Shanghai JiaoTong University, Shanghai, China; and Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai Institute for Pediatric Research, Shanghai, China.
Wei
W
Cai
D020413:3' Untranslated Regions; D015703:Antigens, CD; D001665:Binding Sites; D000067879:CELF1 Protein / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D000067780:ELAV-Like Protein 1 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D010539:Permeability; D014176:Protein Biosynthesis; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D020413:3' Untranslated Regions; D015703:Antigens, CD; C513384:CDH1 protein, human; D000067879:CELF1 Protein; C102843:CELF1 protein, human; D015820:Cadherins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D012333:RNA, Messenger
CUG-binding protein; HU antigen R; processing body