Structural and functional control of the eukaryotic mRNA decapping machinery.

Structural and functional control of the eukaryotic mRNA decapping machinery.
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DOI:
10.1016/j.bbagrm.2012.12.006
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发表时间:
2013-06
影响因子:
4.7
通讯作者:
Song, Haiwei
Song, Haiwei
中科院分区:
生物学2区
文献类型:
--
作者:
Arribas-Layton, Marcos;Wu, Donghui;Lykke-Andersen, Jens;Song, Haiwei

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mRNA降解的调控对基因的正确表达至关重要。mRNA衰变的许多主要途径涉及细胞质中5 ‘ 7-甲基鸟苷(m7G)帽的去除,以允许5 ’到3 '的外核溶解衰变。真核生物脱帽酶中研究最深入和最保守的是Dcp2,其功能是由辅助因子和脱帽增强子辅助的。这些因子中的一部分可以增强Dcp2的催化活性,而其他因子可能会刺激与mRNA底物结合的蛋白质的重塑,否则可能会抑制脱帽。结构研究为Dcp2和脱帽辅助因子激活脱帽的机制提供了重要的见解。额外的mRNA衰变因子可以通过招募脱冠机制的成分来靶向mRNA来发挥作用。mRNA衰变因子、脱盖因子和mRNA底物可以在真核生物中保守的称为P体的细胞质病灶中发现,尽管它们的功能尚不清楚。除Dcp2外,还发现了其他脱帽酶,它们可能补充Dcp2的功能,或在独立的衰变或质量控制途径中起作用。这篇文章是《RNA衰变机制》特刊的一部分。
The regulation of mRNA degradation is critical for proper gene expression. Many major pathways for mRNA decay involve the removal of the 5′ 7-methyl guanosine (m7G) cap in the cytoplasm to allow for 5′-to-3′ exonucleolytic decay. The most well studied and conserved eukaryotic decapping enzyme is Dcp2, and its function is aided by co-factors and decapping enhancers. A subset of these factors can act to enhance the catalytic activity of Dcp2, while others might stimulate the remodeling of proteins bound to the mRNA substrate that may otherwise inhibit decapping. Structural studies have provided major insights into the mechanisms by which Dcp2 and decapping co-factors activate decapping. Additional mRNA decay factors can function by recruiting components of the decapping machinery to target mRNAs. mRNA decay factors, decapping factors, and mRNA substrates can be found in cytoplasmic foci named P bodies that are conserved in eukaryotes, though their function remains unknown. In addition to Dcp2, other decapping enzymes have been identified, which may serve to supplement the function of Dcp2 or act in independent decay or quality control pathways. This article is part of a Special Issue entitled: RNA Decay mechanisms.
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