ACOT7 mRNA level is regulated by Wig1-mediated mRNA decay in premature senescence

초록

RNA-binding proteins (RBPs) are involved in mRNA turnover, transport, translation and stability, and play critical roles in regulating gene expression in response to various signals and stresses. Here, we identified Wig1 as an ionizing radiation (IR)-responsive RBP, based on microarray analysis of cancer cells subjected to IR-induced premature senescence. We next identified the acyl-CoA thioesterase 7 (ACOT7) mRNA as an Wig1 target, based on RT-PCR analysis of immunoprecipitates obtained by using an anti-Wig1 antibody on lysates from cells undergoing IR-induced premature senescence. The ACOT7 mRNA was down- and upregulated in Wig1-overexpressing and Wig1-depleted cells, respectively. MicroRNA-9 was found to associate with the ACOT7 mRNA in a Wig1-dependent manner, and was involved in the Wig1-mediated decay of this target mRNA. Additionally, depletion of ACOT7 resulted in the accumulations of p53 and p21, and subsequent cytostasis. Together, these data indicate that, following IR exposure, Wig1 p53-dependently suppresses ACOT7 expression via miR-9-mediated mRNA decay, and that ACOT7 mediates cell cycle progression by regulating the p53/p21 signaling pathway.