RNA Binding Protein HuR Promotes Autophagosome Formation by Regulating Expression of Autophagy-Related Proteins 5, 12, and 16 in Human Hepatocellular Carcinoma Cells
Authors: Sojin Ahn
Wook Kim
Eun Kyung Lee
Chongtae Kim
Myeongwoo Jung
Sukchan Lee
Hyosun Tak
Eunbyul Ji
Youlim Hong
Hoin Kang
Journal: Molecular and Cellular Biology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: 3′ UTR; RNA binding proteins; translational control.
Affiliations: Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul, South Korea., Department of Genetic Engineering, Sungkyunkwan University, Suwon, South Korea., Department of Molecular Science and Technology, Ajou University, Suwon, South Korea., Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul, South Korea .

Abstract:  Autophagy is a process of lysosomal self-degradation of cellular components by forming autophagosomes. Autophagosome formation is an essential process in autophagy and is fine-tuned by various autophagy-related gene (ATG) products, 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 the RNA binding protein HuR (human antigen R) 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 allows 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 mRNAs by binding to their 3' untranslated regions (UTRs). In addition, we show that HuR expression positively correlates with the levels of ATG5 and ATG12 in hepatocellular carcinoma (HCC) cells. Collectively, our results suggest that HuR functions as a pivotal regulator of autophagosome formation by enhancing the translation of ATG5, ATG12, and ATG16 mRNAs and that augmented expression of HuR and ATGs may participate in the malfunction of autophagy in HCC cells. 

Retracted: No

PubPeer comments:
 In figure 4C, two HuR immunoblots look very similar or identical with each other. Red arrows may find the same streaks in the backgound. ![file] , 
 Thank you for your comment. We investigated the original data and found that incorrect HuR image mistakenly appears in pEGFP-ATG16-3U of Figure 4C. We will do our best to rectify this issue. On the behalf of the authors, I sincerely and deeply apologize for this careless mistake. , 
 2021 correction. https: mcb.asm.org content 41 3 e00643-20 AUTHOR CORRECTION Volume 39, no. 6, e00508-18, 2020, https: doi.org 10.1128 mcb.00508-18. Page 6, Fig. 4C: The HuR Western blot in the pEGFP-ATG16-3U panel was an inadvertent duplicate of that in the pEGFP-ATG12-3U panel. The correct pEGFP-ATG16-3U panel HuR blot should appear as shown below. This correction does not change any conclusions made in the article. We apologize for this error and any confusion it may have caused. ,