Wiegand Heather L, Lu Shihua, Cullen Bryan R
Howard Hughes Medical Institute and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11327-32. doi: 10.1073/pnas.1934877100. Epub 2003 Sep 12.
Intron-containing genes are generally expressed more effectively in human cells than are intronless versions of the same gene. We have asked whether this effect is due directly to splicing or instead reflects the action of components of the exon junction complex (EJC) that is assembled at splice junctions after splicing is completed. Here, we show that intron removal does not enhance gene expression if EJC formation is blocked. Conversely, RNA tethering of the EJC components SRm160 or RNPS1 boosts the expression of intronless mRNAs but not of spliced mRNAs. Splicing and RNPS1 tethering are shown to enhance the same steps in mRNA biogenesis and function, including mRNA 3' end processing and translation. Together, these data argue that the EJC is primarily responsible for the positive effect of splicing on gene expression.
在人类细胞中,含有内含子的基因通常比同一基因的无内含子版本表达得更有效。我们探讨了这种效应是直接归因于剪接,还是相反地反映了外显子连接复合体(EJC)组分的作用,该复合体在剪接完成后于剪接连接处组装而成。在这里,我们表明,如果EJC形成受阻,内含子去除并不会增强基因表达。相反,EJC组分SRm160或RNPS1的RNA拴系会提高无内含子mRNA的表达,但不会提高剪接后mRNA的表达。研究表明,剪接和RNPS1拴系在mRNA生物合成和功能的相同步骤中发挥增强作用,包括mRNA 3'末端加工和翻译。这些数据共同表明,EJC主要负责剪接对基因表达的积极作用。