K63-Ubiquitylation and TRAF6 Pathways Regulate Mammalian P-Body Formation and mRNA Decapping.
K63-Ubiquitylation and TRAF6 Pathways Regulate Mammalian P-Body Formation and mRNA Decapping.
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DOI：
10.1016/j.molcel.2016.05.017
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发表时间：
2016-06
期刊：
影响因子：
16
通讯作者：
U. Tenekeci;M. Poppe;K. Beuerlein;C. Buro;H. Müller;Hendrik Weiser;D. Kettner-Buhrow;Katharina Porada;Doris Newel;Ming Xu;Zhijian J. Chen-Zhijian J.-Chen-2248993093;J. Busch;M. L. Schmitz;M. Kracht
中科院分区：
文献类型：
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作者：
U. Tenekeci;M. Poppe;K. Beuerlein;C. Buro;H. Müller;Hendrik Weiser;D. Kettner-Buhrow;Katharina Porada;Doris Newel;Ming Xu;Zhijian J. Chen-Zhijian J.-Chen-2248993093;J. Busch;M. L. Schmitz;M. Kracht
信号和翻译后修饰调节脱帽mRNA降解途径的步骤是不明确的。在这项研究中，我们揭示了K63连接的泛素化的重要性，通过各种实验方法的去帽因子，P-体的形成和组成性衰变的不稳定的mRNA编码介质的炎症组装。K63分支的泛素链也调节IL-1诱导的P体成分DCP 1a的磷酸化。E3连接酶TRAF 6与DCP 1a结合，间接调节DCP 1a磷酸化、去帽因子表达和基因特异性mRNA衰变。DCP 1a的6个C-末端赖氨酸的突变抑制去帽活性，并损害与mRNA衰变因子DCP 2、EDC 4和XRN 1的相互作用，但不影响EDC 3，从而重塑P体结构。使用泛素链的适当的组装和功能的衰变能力的哺乳动物decapping复合物表明一个额外的控制层，以允许在高等真核生物的decapping活动和mRNA代谢的协调功能。
Signals and posttranslational modifications regulating the decapping step in mRNA degradation pathways are poorly defined. In this study we reveal the importance of K63-linked ubiquitylation for the assembly of decapping factors, P-body formation, and constitutive decay of instable mRNAs encoding mediators of inflammation by various experimental approaches. K63-branched ubiquitin chains also regulate IL-1-inducible phosphorylation of the P-body component DCP1a. The E3 ligase TRAF6 binds to DCP1a and indirectly regulates DCP1a phosphorylation, expression of decapping factors, and gene-specific mRNA decay. Mutation of six C-terminal lysines of DCP1a suppresses decapping activity and impairs the interaction with the mRNA decay factors DCP2, EDC4, and XRN1, but not EDC3, thus remodeling P-body architecture. The usage of ubiquitin chains for the proper assembly and function of the decay-competent mammalian decapping complex suggests an additional layer of control to allow a coordinated function of decapping activities and mRNA metabolism in higher eukaryotes.