title: Arsenite inhibits mRNA deadenylation through proteolytic degradation of Tob and Pan3.
abstract: The poly(A) tail of mRNAs plays pivotal roles in the posttranscriptional control of gene expression at both translation and mRNA stability. Recent findings demonstrate that the poly(A) tail is globally stabilized by some stresses. However, the mechanism underlying this phenomenon has not been elucidated. Here, we show that arsenite-induced oxidative stress inhibits deadenylation of mRNA primarily through downregulation of Tob and Pan3, both of which mediate the recruitment of deadenylases to mRNA. Arsenite selectively induces the proteolytic degradation of Tob and Pan3, and siRNA-mediated knockdown of Tob and Pan3 recapitulates stabilization of the mRNA poly(A) tail observed during arsenite stress. Although arsenite also inhibits translation by activating the eIF2α kinase HRI, arsenite-induced mRNA stabilization can be observed under HRI-depleted conditions. These results highlight the essential role of Tob and Pan3 in the stress-induced global stabilization of mRNA.
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Yamagishi
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Hosoda
authors.affiliation: Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, Japan. Electronic address: hoshino@phar.nagoya-cu.ac.jp.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hoshino
mesh_terms: D020816:Amino Acid Motifs; D018053:Arsenites / Q000737:chemistry*; D002352:Carrier Proteins / Q000378:metabolism*; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D011061:Poly A / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D059748:Proteolysis; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018053:Arsenites; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C568693:PAN3 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C098669:TOB1 protein, human; D025521:Tumor Suppressor Proteins; D011061:Poly A; D046988:Proteasome Endopeptidase Complex; C015001:arsenite
keywords: Deadenylase; Deadenylation; HRI; PAM2; Pan3; Tob