Interaction between HuR and circPABPN1 Modulates Autophagy in the Intestinal Epithelium by Altering ATG16L1 Translation

XX Li, L Xiao, HK Chung, XX Ma, X Liu… - … and cellular biology, 2020 - Taylor & Francis
XX Li, L Xiao, HK Chung, XX Ma, X Liu, JL Song, CZ Jin, JN Rao, M Gorospe, JY Wang
Molecular and cellular biology, 2020Taylor & Francis
Intestinal epithelial autophagy is crucial for host defense against invasive pathogens, and
defects in this process occur frequently in patients with inflammatory bowel disease (IBD)
and other mucosal disorders, but the exact mechanism that activates autophagy is poorly
defined. Here, we investigated the role of RNA-binding protein HuR (human antigen R) in
the posttranscriptional control of autophagy-related genes (ATGs) in the intestinal
epithelium. We found that targeted deletion of HuR in intestinal epithelial cells (IECs) …
Abstract
Intestinal epithelial autophagy is crucial for host defense against invasive pathogens, and defects in this process occur frequently in patients with inflammatory bowel disease (IBD) and other mucosal disorders, but the exact mechanism that activates autophagy is poorly defined. Here, we investigated the role of RNA-binding protein HuR (human antigen R) in the posttranscriptional control of autophagy-related genes (ATGs) in the intestinal epithelium. We found that targeted deletion of HuR in intestinal epithelial cells (IECs) specifically decreased the levels of ATG16L1 in the intestinal mucosa. Intestinal mucosa from patients with IBD exhibited reduced levels of both HuR and ATG16L1. HuR directly interacted with Atg16l1 mRNA via its 3′ untranslated region and enhanced ATG16L1 translation, without affecting Atg16l1 mRNA stability. Circular RNA circPABPN1 blocked HuR binding to Atg16l1 mRNA and lowered ATG16L1 production. HuR silencing in cultured IECs also prevented rapamycin-induced autophagy, which was abolished by overexpressing ATG16L1. These findings indicate that HuR regulates autophagy by modulating ATG16L1 translation via interaction with circPABPN1 in the intestinal epithelium.
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