Department of Molecular Biology, Yokohama City University School of Medicine, 3-9, Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan.
Genes Cells. 2013 Mar;18(3):161-75. doi: 10.1111/gtc.12033. Epub 2013 Jan 28.
SMG-1, a member of the PIKK (phosphoinositide 3-kinase-related kinase) family, plays a critical role in the mRNA quality control system known as nonsense-mediated mRNA decay (NMD). NMD protects cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) which encode nonfunctional or potentially harmful truncated proteins. SMG-1 directly phosphorylates Upf1 helicase, another key component of NMD, upon recognition of PTC on postspliced mRNA during the initial round of translation. Phosphorylated-Upf1 recruits the SMG-5/SMG-7 complex to induce ribosome dissociation and decapping-mediated decay. Phospho-Upf1 also recruits the SMG-6 endonuclease which might be involved in endo-cleavage. Upf1 ATPase/helicase activities are likely required for the activation of other mRNA decay enzymes and the mRNA-protein complex dissociation to complete NMD. At present, a variety of tools are available that can specifically suppress NMD, and it has become possible to examine the contribution of NMD in a variety of physiological and pathological conditions.
SMG-1 是 PIKK（磷脂酰肌醇 3-激酶相关激酶）家族的成员，在被称为无意义介导的 mRNA 降解（NMD）的 mRNA 质量控制系统中发挥着关键作用。NMD 可防止细胞积累具有过早终止密码子（PTC）的异常 mRNA，这些 PTC 编码无功能或潜在有害的截短蛋白。SMG-1 在初始翻译回合中，当识别拼接后 mRNA 上的 PTC 时，直接磷酸化 NMD 的另一个关键组成部分 Upf1 解旋酶。磷酸化的 Upf1 募集 SMG-5/SMG-7 复合物，诱导核糖体解离和脱帽介导的降解。磷酸化的 Upf1 还募集 SMG-6 内切酶，该酶可能参与内切酶切割。Upf1 ATP 酶/解旋酶活性可能是激活其他 mRNA 降解酶和 mRNA-蛋白复合物解离以完成 NMD 所必需的。目前，有多种可特异性抑制 NMD 的工具，这使得研究 NMD 在各种生理和病理条件下的作用成为可能。
