Abstract
RBFOX3, a nuclear RNA-binding protein, is well known as a regulator of alternative pre-mRNA splicing during neuronal development. However, other functions of RBFOX3 are poorly understood. Here, we investigated the function of RBFOX3 in the cytoplasm with respect to regulation of Claudin-1 expression. In human lung tissue, Claudin-1 is higher in RBFOX3-positive cells than in RBFOX3-negative cells. Immunostaining and mRNA quantification revealed that protein levels, but not mRNA levels, of Claudin-1 are increased by RBFOX3. In addition, cycloheximide treatment of human lung cancer cells revealed that RBFOX3 increases the stability of Claudin-1 through attenuation of its ubiquitination. Our study provides insights into the molecular mechanisms by which RBFOX3 regulates Claudin-1 expression in human lung tissue.
Highlights
RNA-binding proteins play important roles in regulation of gene expression by affecting mRNA stability, translation, and miRNA biogenesis, and through formation of splicing networks
Our results demonstrated that RBFOX3 increases the stability of Claudin-1 via regulation of the ubiquitin–proteasome pathway (UPP), which is a novel function of cytoplasmic RBFOX3
We found that CLDN1 is highly expressed in RBFOX3-positive cells of human lung tissues where localization of RBFOX3 is cytoplasmic
Summary
RNA-binding proteins play important roles in regulation of gene expression by affecting mRNA stability, translation, and miRNA biogenesis, and through formation of splicing networks. The mechanisms that regulate Claudin-1 expression and its stability in human lung tissue are unknown. We found that CLDN1 is expressed highly in RBFOX3-positive cells of human lung tissues where localization of RBFOX3 was cytoplasmic.
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