Cho Hana, Han Sisu, Park Ok Hyun, Kim Yoon Ki
Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
Biochim Biophys Acta. 2013 Dec;1829(12):1276-87. doi: 10.1016/j.bbagrm.2013.10.004. Epub 2013 Nov 1.
Suppressor of morphogenesis in genitalia 1 (SMG1), a member of the phosphatidylinositol 3-kinase-related kinase family, is involved in nonsense-mediated mRNA decay (NMD). SMG1 phosphorylates Upf1, a key NMD factor. Subsequently, hyperphosphorylated Upf1 associates with SMG5-7 or proline-rich nuclear receptor coregulatory protein (PNRC2) to elicit rapid mRNA degradation. Upf1 is also known to be involved in staufen 1 (Stau1)-mediated mRNA decay (SMD), which is closely related to NMD. However, the biological and molecular roles of SMG1 in SMD remain unknown. Here, we provide evidence that SMG1 is involved in SMD. The immunoprecipitation results show that SMG1 is complexed with Stau1, Upf1, and Dcp1a. Downregulation of SMG1 or overexpression of a kinase-inactive mutant of SMG1 inhibits SMD efficiency. In addition, downregulation of SMG1 inhibits rapid degradation elicited by artificially tethered Stau1 or Upf1 downstream of the normal termination codon. Furthermore, Stau1 and Upf1 colocalize in processing bodies in an SMG1-dependent manner. We also find that the level of SMG1 increases during adipogenesis. Accordingly, downregulation of SMG1 causes the reduction in the level of Upf1 phosphorylation and delays adipogenesis, suggesting the functional involvement of SMG1 in adipogenesis via SMD.
生殖器官形态发生抑制因子1（SMG1）是磷脂酰肌醇3激酶相关激酶家族的成员，参与无义介导的mRNA降解（NMD）。SMG1使关键的NMD因子Upf1磷酸化。随后，高度磷酸化的Upf1与SMG5 - 7或富含脯氨酸的核受体共调节蛋白（PNRC2）结合，引发mRNA的快速降解。已知Upf1也参与与NMD密切相关的Staufen 1（Stau1）介导的mRNA降解（SMD）。然而，SMG1在SMD中的生物学和分子作用仍然未知。在此，我们提供证据表明SMG1参与SMD。免疫沉淀结果显示SMG1与Stau1、Upf1和Dcp1a形成复合物。SMG1的下调或SMG1激酶失活突变体的过表达会抑制SMD效率。此外，SMG1的下调会抑制正常终止密码子下游人工连接的Stau1或Upf1引发的快速降解。此外，Stau1和Upf1以SMG1依赖的方式共定位于加工小体中。我们还发现，在脂肪生成过程中SMG1的水平会升高。因此，SMG1的下调会导致Upf1磷酸化水平降低，并延迟脂肪生成，这表明SMG1通过SMD在脂肪生成中发挥功能作用。
