Zuber Hélène, Scheer Hélène, Ferrier Emilie, Sement François Michaël, Mercier Pierre, Stupfler Benjamin, Gagliardi Dominique
Institut de Biologie Moléculaire des Plantes, Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, 67000 Strasbourg, France.
Institut de Biologie Moléculaire des Plantes, Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg, 67000 Strasbourg, France.
Cell Rep. 2016 Mar 22;14(11):2707-17. doi: 10.1016/j.celrep.2016.02.060. Epub 2016 Mar 10.
Uridylation emerges as a key modification promoting mRNA degradation in eukaryotes. In addition, uridylation by URT1 prevents the accumulation of excessively deadenylated mRNAs in Arabidopsis. Here, we show that the extent of mRNA deadenylation is controlled by URT1. By using TAIL-seq analysis, we demonstrate the prevalence of mRNA uridylation and the existence, at lower frequencies, of mRNA cytidylation and guanylation in Arabidopsis. Both URT1-dependent and URT1-independent types of uridylation co-exist but only URT1-mediated uridylation prevents the accumulation of excessively deadenylated mRNAs. Importantly, uridylation repairs deadenylated extremities to restore the size distribution observed for non-uridylated oligo(A) tails. In vivo and in vitro data indicate that Poly(A) Binding Protein (PABP) binds to uridylated oligo(A) tails and determines the length of U-extensions added by URT1. Taken together, our results uncover a role for uridylation and PABP in repairing mRNA deadenylated ends and reveal that uridylation plays diverse roles in eukaryotic mRNA metabolism.
尿苷酸化成为促进真核生物mRNA降解的关键修饰。此外,URT1介导的尿苷酸化可防止拟南芥中过度去腺苷酸化的mRNA积累。在此,我们表明mRNA去腺苷酸化的程度受URT1控制。通过TAIL-seq分析,我们证明了拟南芥中mRNA尿苷酸化的普遍性以及较低频率存在的mRNA胞苷酸化和鸟苷酸化。依赖URT1和不依赖URT1的尿苷酸化类型并存,但只有URT1介导的尿苷酸化可防止过度去腺苷酸化的mRNA积累。重要的是,尿苷酸化修复去腺苷酸化的末端,以恢复未尿苷酸化的寡聚(A)尾巴所观察到的大小分布。体内和体外数据表明,聚(A)结合蛋白(PABP)与尿苷酸化的寡聚(A)尾巴结合,并决定URT1添加的U延伸长度。综上所述,我们的结果揭示了尿苷酸化和PABP在修复mRNA去腺苷酸化末端中的作用,并表明尿苷酸化在真核生物mRNA代谢中发挥多种作用。