DAP5与真核起始因子2β（eIF2β）和真核起始因子4A1（eIF4AI）结合，以促进内部核糖体进入位点驱动的翻译。
DAP5 associates with eIF2β and eIF4AI to promote Internal Ribosome Entry Site driven translation.
作者信息
Liberman Noa, Gandin Valentina, Svitkin Yuri V, David Maya, Virgili Geneviève, Jaramillo Maritza, Holcik Martin, Nagar Bhushan, Kimchi Adi, Sonenberg Nahum
机构信息
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 7610001, Israel
Department of Biochemistry, McGill University, Montréal, Québec H3A 1A3, Canada Rosalind and Morris Goodman Cancer Centre, Montréal, Québec H3A 1A3, Canada
出版信息
Nucleic Acids Res. 2015 Apr 20;43(7):3764-75. doi: 10.1093/nar/gkv205. Epub 2015 Mar 16.
Initiation is a highly regulated rate-limiting step of mRNA translation. During cap-dependent translation, the cap-binding protein eIF4E recruits the mRNA to the ribosome. Specific elements in the 5'UTR of some mRNAs referred to as Internal Ribosome Entry Sites (IRESes) allow direct association of the mRNA with the ribosome without the requirement for eIF4E. Cap-independent initiation permits translation of a subset of cellular and viral mRNAs under conditions wherein cap-dependent translation is inhibited, such as stress, mitosis and viral infection. DAP5 is an eIF4G homolog that has been proposed to regulate both cap-dependent and cap-independent translation. Herein, we demonstrate that DAP5 associates with eIF2β and eIF4AI to stimulate IRES-dependent translation of cellular mRNAs. In contrast, DAP5 is dispensable for cap-dependent translation. These findings provide the first mechanistic insights into the function of DAP5 as a selective regulator of cap-independent translation.
起始是mRNA翻译过程中一个受到高度调控的限速步骤。在帽依赖性翻译过程中，帽结合蛋白eIF4E将mRNA招募到核糖体上。一些mRNA的5'非翻译区（5'UTR）中的特定元件，即内部核糖体进入位点（IRESes），可使mRNA直接与核糖体结合，而无需eIF4E。不依赖帽的起始允许在帽依赖性翻译受到抑制的条件下，如应激、有丝分裂和病毒感染时，对一部分细胞和病毒mRNA进行翻译。DAP5是一种eIF4G同源物，有人提出它可调节帽依赖性和不依赖帽的翻译。在此，我们证明DAP5与eIF2β和eIF4AI结合，以刺激细胞mRNA的IRES依赖性翻译。相比之下，DAP5对于帽依赖性翻译是可有可无的。这些发现首次为DAP5作为不依赖帽翻译的选择性调节因子的功能提供了机制上的见解。
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