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真核生物mRNA脱帽机制的结构与功能调控

Structural and functional control of the eukaryotic mRNA decapping machinery.

作者信息

Arribas-Layton Marcos, Wu Donghui, Lykke-Andersen Jens, Song Haiwei

机构信息

University of California, San Diego, La Jolla, CA 92093, USA.

出版信息

Biochim Biophys Acta. 2013 Jun-Jul;1829(6-7):580-9. doi: 10.1016/j.bbagrm.2012.12.006. Epub 2012 Dec 31.

Abstract

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 (m(7)G) 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.

摘要

mRNA降解的调控对于基因的正常表达至关重要。许多mRNA衰变的主要途径涉及在细胞质中去除5' 7-甲基鸟苷(m(7)G)帽,以允许5'至3'核酸外切酶衰变。研究最充分且保守的真核去帽酶是Dcp2,其功能由辅助因子和去帽增强子协助。这些因子的一个子集可以增强Dcp2的催化活性,而其他因子可能刺激与mRNA底物结合的蛋白质的重塑,否则这些蛋白质可能会抑制去帽。结构研究为Dcp2和去帽辅助因子激活去帽的机制提供了重要见解。其他mRNA衰变因子可以通过将去帽机制的成分募集到靶向mRNA来发挥作用。mRNA衰变因子、去帽因子和mRNA底物可以在真核生物中保守的名为P小体的细胞质焦点中找到,尽管它们的功能仍然未知。除了Dcp2之外,还鉴定出了其他去帽酶,它们可能用于补充Dcp2的功能,或在独立的衰变或质量控制途径中发挥作用。本文是名为:RNA衰变机制的特刊的一部分。

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