A widespread alternate form of cap-dependent mRNA translation initiation.
A widespread alternate form of cap-dependent mRNA translation initiation.
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DOI：
10.1038/s41467-018-05539-0
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发表时间：
2018-08-03
影响因子：
16.6
通讯作者：
Schneider RJ
中科院分区：
文献类型：
--
作者：
de la Parra C;Ernlund A;Alard A;Ruggles K;Ueberheide B;Schneider RJ
大多数哺乳动物mRNA的翻译起始是由结合真核起始因子4 E（eIF 4 E）的5′帽结构介导的。然而，eIF 4 E的失活不会损害许多加帽mRNA的翻译，这表明对于帽依赖性但eIF 4 E非依赖性翻译可能存在未知的替代机制。我们发现DAP 5是一种缺乏eIF 4 E结合的eIF 4GI同源物，它利用eIF 3d促进大约20%的mRNA的帽依赖性翻译。全基因组转录组学和翻译组学分析表明，DAP 5是许多转录因子和受体加帽mRNA及其mRNA靶点翻译所必需的，这些mRNA靶点涉及细胞存活、运动、DNA修复和翻译起始等mRNA。质谱和交联研究表明，eIF 3d是DAP 5的直接结合伴侣。体外翻译和核糖体复合物的研究表明，DAP 5和eIF 3d都是必不可少的eIF 4 E-独立的加帽mRNA翻译。这些研究揭示了DAP 5-eIF 3d复合物的帽依赖性mRNA翻译的广泛和先前未知的机制。eIF 4 E与mRNA 5′端帽的结合是典型翻译起始的关键早期步骤，但对eIF 4 E的要求并不普遍。在这里，作者表明eIF 4G同源物DAP 5与eIF 3相互作用，以eIF 4 E非依赖性方式促进大量mRNA的帽依赖性翻译。
Translation initiation of most mammalian mRNAs is mediated by a 5′ cap structure that binds eukaryotic initiation factor 4E (eIF4E). However, inactivation of eIF4E does not impair translation of many capped mRNAs, suggesting an unknown alternate mechanism may exist for cap-dependent but eIF4E-independent translation. We show that DAP5, an eIF4GI homolog that lacks eIF4E binding, utilizes eIF3d to facilitate cap-dependent translation of approximately 20% of mRNAs. Genome-wide transcriptomic and translatomic analyses indicate that DAP5 is required for translation of many transcription factors and receptor capped mRNAs and their mRNA targets involved in cell survival, motility, DNA repair and translation initiation, among other mRNAs. Mass spectrometry and crosslinking studies demonstrate that eIF3d is a direct binding partner of DAP5. In vitro translation and ribosome complex studies demonstrate that DAP5 and eIF3d are both essential for eIF4E-independent capped-mRNA translation. These studies disclose a widespread and previously unknown mechanism for cap-dependent mRNA translation by DAP5-eIF3d complexes. Binding of eIF4E to the 5′ cap of mRNAs is a key early step in canonical translation initiation, but the requirement for eIF4E is not universal. Here the authors show that the eIF4G homolog DAP5 interacts with eIF3 to promote cap-dependent translation of a significant number of mRNA in an eIF4E-independent manner.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
8
作者：
Weingarten-Gabbay, S.;Khan, D.;Kimchi, A.
通讯作者：
Kimchi, A.
影响因子：
5.3
作者：
Svitkin, YV;Herdy, B;Sonenberg, N
通讯作者：
Sonenberg, N
影响因子：
14.9
作者：
Liberman N;Gandin V;Svitkin YV;David M;Virgili G;Jaramillo M;Holcik M;Nagar B;Kimchi A;Sonenberg N
通讯作者：
Sonenberg N
影响因子：
64.5
作者：
Sonenberg N;Hinnebusch AG
通讯作者：
Hinnebusch AG