Division of Cytogenetics, National Institute of Genetics, Mishima, 1111 Yata, Mishima 411-8540, Japan.
Biochem Biophys Res Commun. 2012 Oct 12;427(1):143-7. doi: 10.1016/j.bbrc.2012.09.027. Epub 2012 Sep 16.
Ago1, an effector protein of RNA interference (RNAi), regulates heterochromatin silencing and cell cycle arrest in fission yeast. However, the mechanism by which Ago1 controls cell cycle checkpoint following hydroxyurea (HU) treatment has not been elucidated. In this study, we show that Ago1 and other RNAi factors control cell cycle checkpoint following HU treatment via a mechanism independent of silencing. While silencing requires dcr1(+), the overexpression of ago1(+) alleviated the cell cycle defect in dcr1Δ. Ago1 interacted with the mRNA export factor, Ptr1. The ptr1-1 mutation impaired cell cycle checkpoint but gene silencing was unaffected. Genetic analysis revealed that the regulation of cell cycle checkpoint by ago1(+) is dependent on ptr1(+). Nuclear accumulation of poly(A)(+) RNAs was detected in mutants of ago1(+) and ptr1(+), suggesting there is a functional link between the cell cycle checkpoint and RNAi-mediated RNA quality control.
AGO1，RNA 干扰（RNAi）的效应蛋白，调节有丝分裂酵母中的异染色质沉默和细胞周期停滞。然而，AGO1 如何在羟基脲（HU）处理后控制细胞周期检查点尚不清楚。在这项研究中，我们表明 AGO1 和其他 RNAi 因子通过一种不依赖沉默的机制控制 HU 处理后的细胞周期检查点。虽然沉默需要 dcr1(+)，但 ago1(+)的过表达缓解了 dcr1Δ 的细胞周期缺陷。AGO1 与 mRNA 输出因子 Ptr1 相互作用。ptr1-1 突变会损害细胞周期检查点，但基因沉默不受影响。遗传分析表明，ago1(+)对细胞周期检查点的调节依赖于 ptr1(+)。AGO1 和 ptr1(+)突变体中检测到多（A）（+) RNA 的核积累，表明细胞周期检查点和 RNAi 介导的 RNA 质量控制之间存在功能联系。
