Small noncoding vault RNA2 ‐1 disrupts gut epithelial barrier function via interaction with HuR

Autor: Xiang‐Xue Ma, Lan Xiao, Susan J Wen, Ting‐Xi Yu, Shweta Sharma, Hee K Chung, Bridgette Warner, Caroline G Mallard, Jaladanki N Rao, Myriam Gorospe, Jian‐Ying Wang
Rok vydání: 2022
Předmět:
Zdroj: EMBO reports. 24
ISSN: 1469-3178
1469-221X
Popis: Vault RNAs (vtRNAs) are small noncoding RNAs and highly expressed in many eukaryotes. Here, we identified vtRNA2-1 as a novel regulator of the intestinal barrier via interaction with RNA-binding protein HuR. Intestinal mucosal tissues from patients with inflammatory bowel diseases and from mice with colitis or sepsis express increased levels of vtRNAs relative to controls. Ectopically expressed vtRNA2-1 decreases the levels of intercellular junction (IJ) proteins claudin 1, occludin, and E-cadherin and causes intestinal epithelial barrier dysfunction in vitro, whereas vtRNA2-1 silencing promotes barrier function. Increased vtRNA2-1 also decreases IJs in intestinal organoid, inhibits epithelial renewal, and causes Paneth cell defects ex vivo. Elevating the levels of tissue vtRNA2-1 in the intestinal mucosa increases the vulnerability of the gut barrier to septic stress in mice. vtRNA2-1 interacts with HuR and prevents HuR binding to claudin 1 and occludin mRNAs, thus decreasing their translation. These results indicate that vtRNA2-1 impairs intestinal barrier function by repressing HuR-facilitated translation of claudin 1 and occludin.
Databáze: OpenAIRE
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