The Exon Junction Complex Core Represses Cancer-Specific Mature mRNA Re-splicing: A Potential Key Role in Terminating Splicing.
The Exon Junction Complex Core Represses Cancer-Specific Mature mRNA Re-splicing: A Potential Key Role in Terminating Splicing.
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DOI：
10.3390/ijms22126519
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发表时间：
2021-06-17
影响因子：
5.6
通讯作者：
Mayeda A
中科院分区：
文献类型：
--
作者：
Otani Y;Fujita KI;Kameyama T;Mayeda A
使用TSG 101前mRNA，我们先前发现了癌症特异性的成熟mRNA再剪接，产生异常转录物/蛋白质。mRNA在各种癌细胞中异常再剪接的事实意味着必须存在重要的机制来防止正常细胞中剪接的mRNA上的有害再剪接。因此，我们假设mRNA再剪接是由特定的阻遏物控制，我们通过基于siRNA的mRNA再剪接活性筛选来寻找阻遏物候选物。我们发现，EIF 4A 3，这是一个外显子连接复合物（EJC）的核心组成部分，敲低，显着促进mRNA的重新剪接。值得注意的是，我们可以通过敲低任何核心EJC蛋白，EIF 4A 3，MAGOH或RBM 8A（Y14）来重现正常细胞中的癌症特异性mRNA再剪接，这表明EJC核心是癌细胞中经常观察到的mRNA再剪接的阻遏物。我们认为EJC核心是防止成熟mRNA过度剪接的关键mRNA质量控制因素。
Using TSG101 pre-mRNA, we previously discovered cancer-specific re-splicing of mature mRNA that generates aberrant transcripts/proteins. The fact that mRNA is aberrantly re-spliced in various cancer cells implies there must be an important mechanism to prevent deleterious re-splicing on the spliced mRNA in normal cells. We thus postulated that mRNA re-splicing is controlled by specific repressors, and we searched for repressor candidates by siRNA-based screening for mRNA re-splicing activity. We found that knock-down of EIF4A3, which is a core component of the exon junction complex (EJC), significantly promoted mRNA re-splicing. Remarkably, we could recapitulate cancer-specific mRNA re-splicing in normal cells by knock-down of any of the core EJC proteins, EIF4A3, MAGOH, or RBM8A (Y14), implicating the EJC core as the repressor of mRNA re-splicing often observed in cancer cells. We propose that the EJC core is a critical mRNA quality control factor to prevent over-splicing of mature mRNA.
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