The autophagy initiation factor ATG13 mRNA is stabilized by the RNA-binding protein YBX3.

Abstract

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.