RNA binding protein HuR promotes autophagosome formation by regulating expressions of autophagy-related protein 5, 12, and 16 in human hepatocellular carcinoma cells.

Autophagy is a lysosomal self-degradation process of cellular components by forming autophagosomes. Autophagosome formation is an essential process in autophagy, and is fine-tuned by various autophagy-related gene (ATG) molecules including ATG5, ATG12, and ATG16. Although several reports have shown that numerous factors affect multiple levels of gene regulation to orchestrate cellular autophagy, the detailed mechanism of autophagosome formation still needs further investigation. In this study, we demonstrate that RNA binding protein HuR performs an essential function in autophagosome formation. We observe that HuR silencing leads to inhibition of autophagosome formation and autophagic flux in liver cells. Ribonucleoprotein immunoprecipitation (RIP) assay allow the identification of ATG5 , ATG12 , and ATG16 mRNAs as the direct targets of HuR. We further show that HuR mediates the translation of ATG5 , ATG12 , and ATG16 mRNA by binding to their 3'UTR. In addition, we show that HuR expression positively correlates with the levels of ATG5 and ATG12 in hepatocellular carcinoma. Collectively, our results suggest that HuR functions as a pivotal regulator of autophagosome formation by enhancing the translation of ATG5 , ATG12 , and ATG16 mRNA and augmented expression of HuR and ATGs may participate in the malfunction of autophagy in hepatocellular carcinoma cells.