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Long noncoding RNA SPRY4-IT1 regulates intestinal epithelial barrier function by
modulating the expression levels of tight junction proteins
#MMPMID26680741
Xiao L
; Rao JN
; Cao S
; Liu L
; Chung HK
; Zhang Y
; Zhang J
; Liu Y
; Gorospe M
; Wang JY
Mol Biol Cell
2016[Feb]; 27
(4
): 617-26
PMID26680741
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Epithelial cells line the intestinal mucosa and form an important barrier to a
wide array of noxious substances in the lumen. Disruption of the barrier
integrity occurs commonly in various pathologies. Long noncoding RNAs (lncRNAs)
control diverse biological processes, but little is known about the role of
lncRNAs in regulation of the gut permeability. Here we show that the lncRNA
SPRY4-IT1 regulates the intestinal epithelial barrier function by altering
expression of tight junction (TJ) proteins. SPRY4-IT1 silencing led to
dysfunction of the epithelial barrier in cultured cells by decreasing the
stability of mRNAs encoding TJ proteins claudin-1, claudin-3, occludin, and JAM-1
and repressing their translation. In contrast, increasing the levels of SPRY4-IT1
in the intestinal mucosa protected the gut barrier in mice exposed to septic
stress by increasing the abundance of TJ proteins. SPRY4-IT1 directly interacted
with TJ mRNAs, and this process was enhanced through the association with the
RNA-binding protein HuR. Of interest, the intestinal mucosa from patients with
increased gut permeability exhibited a decrease in the levels of SPRY4-IT1. These
findings highlight a novel role for SPRY4-IT1 in controlling the intestinal
epithelial barrier and define a mechanism by which SPRY4-IT1 modulates TJ
expression by altering the stability and translation of TJ mRNAs.
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