title: Reduction of AUF1-mediated follistatin mRNA decay during glucose starvation protects cells from apoptosis.
abstract: Follistatin (FST) performs several vital functions in the cells, including protection from apoptosis during stress. The expression of FST is up-regulated in response to glucose deprivation by an unknown mechanism. We herein showed that the induction of FST by glucose deprivation was due to an increase in the half-life of its mRNA. We further identified an AU-rich element (ARE) in the 3'UTR of FST mRNA that mediated its decay. The expression of FST was elevated after knocking down AUF1 and reduced when AUF1 was further expressed. In vitro binding assays and RNA pull-down assays revealed that AUF1 interacted with FST mRNA directly via its ARE. During glucose deprivation, a majority of AUF1 shuttled from cytoplasm to nucleus, resulting in dissociation of AUF1 from FST mRNA and thus stabilization of FST mRNA. Finally, knockdown of AUF1 decreased whereas overexpression of AUF1 increased glucose deprivation-induced apoptosis. The apoptosis promoting effect of AUF1 was eliminated in FST expressing cells. Collectively, this study provided evidence that AUF1 is a negative regulator of FST expression and participates in the regulation of cell survival under glucose deprivation.
authors.affiliation: Institute of Environmental Medicine, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China Program in Molecular Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China xiangweigao@gmail.com xiangweigao@zju.edu.cn.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Environmental Medicine, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China Program in Molecular Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Dong
authors.affiliation: Institute of Environmental Medicine, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China Program in Molecular Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.affiliation: Institute of Environmental Medicine, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China Program in Molecular Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Jinghao
authors.initials: J
authors.lastname: Sheng
authors.affiliation: Institute of Environmental Medicine, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Institute of Environmental Medicine, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Su
authors.affiliation: Institute of Environmental Medicine, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China Program in Molecular Cell Biology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou 310058, China zpxu@zju.edu.cn.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D038681:Follistatin / Q000235:genetics* / Q000378:metabolism; D005947:Glucose / Q000502:physiology*; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D006801:Humans; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D038681:Follistatin; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D012333:RNA, Messenger; D055372:AMP-Activated Protein Kinases; D005947:Glucose