SMG1 regulates adipogenesis via targeting of staufenl-mediated mRNA decay
SMG1 regulates adipogenesis via targeting of staufenl-mediated mRNA decay
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DOI：
10.1016/j.bbagrm.2013.10.004
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发表时间：
2013-12-01
影响因子：
4.7
通讯作者：
Kim, Yoon Ki
中科院分区：
文献类型：
--
作者：
Cho, Hana;Han, Sisu;Kim, Yoon Ki
生殖器形态发生抑制因子I（SMG 1）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衰变（NMD）。SMG 1磷酸化Upf 1，一个关键的NMD因子。随后，过度磷酸化的Upf 1与SMG 5 -7或富含脯氨酸的核受体辅调节蛋白（PNRC 2）结合，引起快速mRNA降解。已知Upf 1也参与Staufen 1（Stau 1）介导的mRNA衰变（SMD），这与NMD密切相关。然而，SMG 1在SMD中的生物学和分子作用仍然未知。在这里，我们提供了SMG 1参与SMD的证据。免疫沉淀结果显示SMG 1与Stau 1、Upf 1和Dcp 1a复合SMG 1的下调或SMG 1的激酶失活突变体的过表达抑制SMD效率。此外，SMG 1的下调抑制了由正常终止密码子下游人工拴系的Stau 1或Upf 1引起的快速降解。此外，Stau 1和Upf 1以SMG 1依赖的方式在处理体中共定位。我们还发现SMG 1的水平在脂肪形成过程中增加。因此，SMG 1的下调导致Upf 1磷酸化水平降低并延迟脂肪形成，表明SMG 1通过SMD参与脂肪形成的功能。(C)2013爱思唯尔有限公司版权所有。
Suppressor of morphogenesis in genitalia I (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 immuno-precipitation 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. (C) 2013 Elsevier B.V. All rights reserved.