剪接增强哺乳动物细胞中的翻译：外显子连接复合体的额外功能。
Splicing enhances translation in mammalian cells: an additional function of the exon junction complex.
作者信息
Nott Ajit, Le Hir Hervé, Moore Melissa J
机构信息
Howard Hughes Medical Institute, Department of Biochemistry, Brandeis University, Waltham, MA 02454, USA.
出版信息
Genes Dev. 2004 Jan 15;18(2):210-22. doi: 10.1101/gad.1163204.
Abstract
In mammalian cells, spliced mRNAs yield greater quantities of protein per mRNA molecule than do otherwise identical mRNAs not made by splicing. This increased translational yield correlates with enhanced cytoplasmic polysome association of spliced mRNAs, and is attributable to deposition of exon junction complexes (EJCs). Translational stimulation can be replicated by tethering the EJC proteins Y14, Magoh, and RNPS1 or the nonsense-mediated decay (NMD) factors Upf1, Upf2, and Upf3b to an intronless reporter mRNA. Thus, in addition to its previously characterized role in NMD, the EJC also promotes mRNA polysome association. Furthermore, the ability to stimulate translation when bound inside an open reading frame appears to be a general feature of factors required for NMD.
摘要
在哺乳动物细胞中，经过剪接的mRNA每分子产生的蛋白质数量比未经剪接但其他方面相同的mRNA更多。这种翻译产量的增加与剪接后mRNA在细胞质中与多核糖体的结合增强相关，并且归因于外显子连接复合体（EJC）的沉积。通过将EJC蛋白Y14、Magoh和RNPS1或无义介导的衰变（NMD）因子Upf1、Upf2和Upf3b拴系到无内含子的报告mRNA上，可以复制翻译刺激。因此，除了其先前在NMD中所表征的作用外，EJC还促进mRNA与多核糖体的结合。此外，当结合在开放阅读框内时刺激翻译的能力似乎是NMD所需因子的一个普遍特征。
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1
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Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11327-32. doi: 10.1073/pnas.1934877100. Epub 2003 Sep 12.
2
An evolutionarily conserved role for SRm160 in 3'-end processing that functions independently of exon junction complex formation.SRm160在3'端加工中具有进化保守作用，该作用独立于外显子连接复合体的形成。
J Biol Chem. 2003 Nov 7;278(45):44153-60. doi: 10.1074/jbc.M306856200. Epub 2003 Aug 27.
3
A novel mode of RBD-protein recognition in the Y14-Mago complex.Y14-Mago复合物中RBD-蛋白识别的一种新模式。
Nat Struct Biol. 2003 Jun;10(6):433-9. doi: 10.1038/nsb926.
4
Y14 and hUpf3b form an NMD-activating complex.Y14和hUpf3b形成一种NMD激活复合物。
Mol Cell. 2003 Apr;11(4):939-49. doi: 10.1016/s1097-2765(03)00142-4.
5
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Trends Biochem Sci. 2003 Apr;28(4):215-20. doi: 10.1016/S0968-0004(03)00052-5.
6
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7
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RNA. 2003 May;9(5):607-17. doi: 10.1261/rna.5250403.
8
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9
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10
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