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Autophagy, a highly conserved form of cellular recycling, is essential for cellular homeostasis. Its dysregulation has been linked to neurodegenerative diseases and various cancers, including breast cancer. We set out to determine if the RNA‐binding protein (RBP) YBX3 regulates autophagy mRNAs, as previous findings suggest YBX3 depletion reduces distinct autophagy transcripts. We found that YBX3 interacts with and stabilizes the mRNA of the autophagy initiation factor ATG13 in HeLa, which in turn increases ATG13 protein expression. We have shown that this requires the 3′ untranslated region (UTR) of ATG13 and occurs in other human cell lines, including HEK293, HepG2, and HCT116. Together, our data suggest a novel regulatory role for YBX3 of autophagy initiation through posttranscriptional control of ATG13 mRNA stability. [ABSTRACT FROM AUTHOR]

Fibrosing cholangiopathies, including biliary atresia and primary sclerosing cholangitis, involve immune-mediated bile duct epithelial injury and hepatic bile acid (BA) retention (cholestasis). Regulatory T-cells (Tregs) can prevent auto-reactive lymphocyte activation, yet the effects of BA on this CD4 lymphocyte subset are unknown. Gene regulatory networks for hepatic CD4 lymphocytes in a murine cholestasis model revealed Tregs are polarized to Th17 during cholestasis. Following bile duct ligation, Stat3 deletion in CD4 lymphocytes preserved hepatic Treg responses. While pharmacological reduction of hepatic BA in MDR2-/- mice prompted Treg expansion and diminished liver injury, this improvement subsided with Treg depletion. A cluster of patients diagnosed with biliary atresia showed both increased hepatic Treg responses and improved 2-year native liver survival, supporting that Tregs might protect against neonatal bile duct obstruction. Together, these findings suggest liver BA determine Treg function and should be considered as a therapeutic target to restore protective hepatic immune responses.