Slevin Michael K, Gourronc Francoise, Hartley Rebecca S
Molecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242, USA.
Nucleic Acids Res. 2007;35(7):2167-76. doi: 10.1093/nar/gkm084. Epub 2007 Mar 13.
The early cell divisions of Xenopus laevis and other metazoan embryos occur in the presence of constitutively high levels of the cell cycle regulator cyclin E1. Upon completion of the 12th cell division, a time at which many maternal proteins are downregulated by deadenylation and destabilization of their encoding mRNAs, maternal cyclin E1 protein is downregulated while its mRNA is polyadenylated and stable. We report here that stable polyadenylation of cyclin E1 mRNA requires three cis-acting elements in the 3' untranslated region; the nuclear polyadenylation sequence, a contiguous cytoplasmic polyadenylation element and an upstream AU-rich element. ElrA, the Xenopus homolog of HuR and a member of the ELAV gene family binds the cyclin E1 3'UTR with high affinity. Deletion of these elements dramatically reduces the affinity of ElrA for the cyclin E1 3'UTR, abolishes polyadenylation and destabilizes the mRNA. Together, these findings provide compelling evidence that ElrA functions in polyadenylation and stabilization of cyclin E1 mRNA via binding these elements.
非洲爪蟾和其他后生动物胚胎的早期细胞分裂是在细胞周期调节因子细胞周期蛋白E1持续高水平存在的情况下发生的。在第12次细胞分裂完成时，许多母体蛋白因编码mRNA的去腺苷酸化和不稳定而下调，母体细胞周期蛋白E1蛋白下调，而其mRNA被多聚腺苷酸化并保持稳定。我们在此报告，细胞周期蛋白E1 mRNA的稳定多聚腺苷酸化需要3'非翻译区中的三个顺式作用元件；核多聚腺苷酸化序列、相邻的细胞质多聚腺苷酸化元件和上游富含AU的元件。非洲爪蟾HuR的同源物、ELAV基因家族成员ElrA与细胞周期蛋白E1 3'UTR具有高亲和力。删除这些元件会显著降低ElrA对细胞周期蛋白E1 3'UTR的亲和力，消除多聚腺苷酸化并使mRNA不稳定。这些发现共同提供了令人信服的证据，表明ElrA通过结合这些元件在细胞周期蛋白E1 mRNA的多聚腺苷酸化和稳定中发挥作用。
