内含子Alus影响可变剪接
Intronic Alus Influence Alternative Splicing
摘要：
对人类转录组的检查显示，RNA编辑水平高于迄今为止测试的任何其他生物。这表明在人类转录组内广泛的双链RNA（dsRNA）形成。大多数编辑位点位于灵长类特有的称为Alu的逆转录元件中。在内含子序列中发现了大部分Alus，这意味着mRNA前体中广泛的Alu dsRNA形成。然而，这些内含子Alus对侧翼外显子剪接的影响在很大程度上是未知的。在这里，我们表明，更多的Alus侧翼选择性剪接的外显子比组成性剪接的，这是特别值得注意的那些外显子，已经改变了他们的剪接模式，从组成的替代在人类进化过程中。这意味着Alu的插入可能会改变侧翼外显子的剪接模式。事实上，我们通过实验证明，两个Alu元件以相反的方向插入内含子中进行碱基配对，如RNA编辑所示，并影响下游外显子的剪接模式，将其从组成型转变为替代型。我们的研究结果表明内含子Alus在影响侧翼外显子剪接中的重要性，进一步强调了Alus在人类转录组形成中的作用
英文摘要：
Examination of the human transcriptome reveals higher levels of RNA editing than in any other organism tested to date. This is indicative of extensive double-stranded RNA (dsRNA) formation within the human transcriptome. Most of the editing sites are located in the primate-specific retrotransposed element called Alu. A large fraction of Alus are found in intronic sequences, implying extensive Alu-Alu dsRNA formation in mRNA precursors. Yet, the effect of these intronic Alus on splicing of the flanking exons is largely unknown. Here, we show that more Alus flank alternatively spliced exons than constitutively spliced ones; this is especially notable for those exons that have changed their mode of splicing from constitutive to alternative during human evolution. This implies that Alu insertions may change the mode of splicing of the flanking exons. Indeed, we demonstrate experimentally that two Alu elements that were inserted into an intron in opposite orientation undergo base-pairing, as evident by RNA editing, and affect the splicing patterns of a downstream exon, shifting it from constitutive to alternative. Our results indicate the importance of intronic Alus in influencing the splicing of flanking exons, further emphasizing the role of Alus in shaping of the human transcriptome
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