The Exon Junction Complex Controls the Splicing of mapk and Other Long Intron-Containing Transcripts in Drosophila
The Exon Junction Complex Controls the Splicing of mapk and Other Long Intron-Containing Transcripts in Drosophila
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DOI：
10.1016/j.cell.2010.09.014
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发表时间：
2010-10-15
期刊：
影响因子：
64.5
通讯作者：
Therrien, Marc
中科院分区：
文献类型：
--
作者：
Ashton-Beaucage, Dariel;Udell, Christian M.;Therrien, Marc
信号传导途径由大量翻译后机制控制。相比之下，人们对调节其核心成分表达的机制知之甚少。我们在果蝇中进行了 RNAi 筛选，寻找调节 RAS/MAPK 信号传导的因子，并确定外显子连接复合体 (EJC) 是该途径的关键元件。 EJC 结合 mRNA 的外显子-外显子连接，迄今为止，仅与剪接后事件相关。在这里，我们报告 EJC 是通过明显控制外显子定义的机制来正确剪接 mapk 转录本所必需的。此外，EJC耗尽细胞的全转录组和RT-PCR分析表明，包含长内含子的基因（包括mapk）的剪接对EJC活性敏感。这些结果确定了 EJC 在转录子子集剪接中的作用，并表明 RAS/MAPK 信号传导依赖于 EJC 对 MAPK 水平的调节。
Signaling pathways are controlled by a vast array of posttranslational mechanisms. By contrast, little is known regarding the mechanisms that regulate the expression of their core components. We conducted an RNAi screen in Drosophila for factors modulating RAS/MAPK signaling and identified the Exon Junction Complex (EJC) as a key element of this pathway. The EJC binds the exon-exon junctions of mRNAs and thus far, has been linked exclusively to post-splicing events. Here, we report that the EJC is required for proper splicing of mapk transcripts by a mechanism that apparently controls exon definition. Moreover, whole transcriptome and RT-PCR analyses of EJC-depleted cells revealed that the splicing of long intron-containing genes, which includes mapk, is sensitive to EJC activity. These results identify a role for the EJC in the splicing of a subset of transcripts and suggest that RAS/MAPK signaling depends on the regulation of MAPK levels by the EJC.