Hosoda Nao, Kobayashi Tetsuo, Uchida Naoyuki, Funakoshi Yuji, Kikuchi Yoshiko, Hoshino Shinichi, Katada Toshiaki
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
J Biol Chem. 2003 Oct 3;278(40):38287-91. doi: 10.1074/jbc.C300300200. Epub 2003 Aug 15.
Messenger RNA decay, which is a regulated process intimately linked to translation, begins with the deadenylation of the poly(A) tail at the 3' end. However, the precise mechanism triggering the first step of mRNA decay and its relationship to translation have not been elucidated. Here, we show that the translation termination factor eRF3 mediates mRNA deadenylation and decay in the yeast Saccharomyces cerevisiae. The N-domain of eRF3, which is not necessarily required for translation termination, interacts with the poly(A)-binding protein PABP. When this interaction is blocked by means of deletion or overexpression of the N-domain of eRF3, half-lives of all mRNAs are prolonged. The eRF3 mutant lacking the N-domain is deficient in the poly(A) shortening. Furthermore, the eRF3-mediated mRNA decay requires translation to proceed, especially ribosomal transition through the termination codon. These results indicate that the N-domain of eRF3 mediates mRNA decay by regulating deadenylation in a manner coupled to translation.
信使核糖核酸（mRNA）衰变是一个与翻译密切相关的受调控过程，始于3'端多聚腺苷酸（poly(A)）尾的去腺苷酸化。然而，触发mRNA衰变第一步的精确机制及其与翻译的关系尚未阐明。在此，我们表明翻译终止因子eRF3介导酿酒酵母中的mRNA去腺苷酸化和衰变。eRF3的N结构域对于翻译终止并非必需，它与多聚腺苷酸结合蛋白PABP相互作用。当通过删除或过表达eRF3的N结构域来阻断这种相互作用时，所有mRNA的半衰期都会延长。缺少N结构域的eRF3突变体在poly(A)缩短方面存在缺陷。此外，eRF3介导的mRNA衰变需要翻译进行，特别是核糖体通过终止密码子的转换。这些结果表明，eRF3的N结构域通过以与翻译偶联的方式调节去腺苷酸化来介导mRNA衰变。
