Human eIF3b and eIF3a serve as the nucleation core for the assembly of eIF3 into two interconnected modules: the yeast-like core and the octamer.
Human eIF3b and eIF3a serve as the nucleation core for the assembly of eIF3 into two interconnected modules: the yeast-like core and the octamer.
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DOI：
10.1093/nar/gkw972
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发表时间：
2016-12-15
影响因子：
14.9
通讯作者：
Valášek LS
中科院分区：
文献类型：
--
作者：
Wagner S;Herrmannová A;Šikrová D;Valášek LS
12亚基哺乳动物eIF3是最大和最复杂的翻译起始因子，并且已经涉及翻译起始、终止和核糖体再循环的许多步骤。在各种类型的癌症和发育障碍中观察到不平衡的eIF3表达水平，但改变eIF3亚基表达对其整体结构和组成以及一般翻译的影响仍不清楚。我们提出了第一个完整的体内研究监测RNAi敲低人eIF3的每个亚基对其功能，亚基平衡和完整性的影响。我们发现，eIF3b和八聚体eIF3a亚基作为成核核心周围的其他亚基组装成两个相互连接的模块：酵母样核心和八聚体，分别。在缺乏eIF3b的情况下，两个模块在体内都不形成，而eIF3d敲低导致严重的增殖缺陷，对eIF3完整性没有影响。破坏八聚体产生一系列在翻译调控中具有潜在作用的亚复合物。这项研究概述了eIF3组装的机制，并说明了eIF3亚基的不平衡表达如何影响因子的整体表达谱，从而为人类eIF3复合体以及eIF3失调与癌症之间的关系提供了全面的指导。
The 12-subunit mammalian eIF3 is the largest and most complex translation initiation factor and has been implicated in numerous steps of translation initiation, termination and ribosomal recycling. Imbalanced eIF3 expression levels are observed in various types of cancer and developmental disorders, but the consequences of altered eIF3 subunit expression on its overall structure and composition, and on translation in general, remain unclear. We present the first complete in vivo study monitoring the effects of RNAi knockdown of each subunit of human eIF3 on its function, subunit balance and integrity. We show that the eIF3b and octameric eIF3a subunits serve as the nucleation core around which other subunits assemble in an ordered way into two interconnected modules: the yeast-like core and the octamer, respectively. In the absence of eIF3b neither module forms in vivo, whereas eIF3d knock-down results in severe proliferation defects with no impact on eIF3 integrity. Disrupting the octamer produces an array of subcomplexes with potential roles in translational regulation. This study, outlining the mechanism of eIF3 assembly and illustrating how imbalanced expression of eIF3 subunits impacts the factor's overall expression profile, thus provides a comprehensive guide to the human eIF3 complex and to the relationship between eIF3 misregulation and cancer.
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影响因子：
4.5
作者：
Kolupaeva, VG;Unbehaun, A;Pestova, TV
通讯作者：
Pestova, TV
影响因子：
64.5
作者：
Meyer KD;Patil DP;Zhou J;Zinoviev A;Skabkin MA;Elemento O;Pestova TV;Qian SB;Jaffrey SR
通讯作者：
Jaffrey SR
影响因子：
5.6
作者：
Elantak L;Wagner S;Herrmannová A;Karásková M;Rutkai E;Lukavsky PJ;Valásek L
通讯作者：
Valásek L
影响因子：
14.9
作者：
Gunišová S;Valášek LS
通讯作者：
Valášek LS
DOI：
10.1261/rna.054452.115
发表时间：
2016-03
期刊：
RNA (New York, N.Y.)
影响因子：
--
作者：
Beznosková P;Gunišová S;Valášek LS
通讯作者：
Valášek LS