Splicing repression allows the gradual emergence of new Alu-exons in primate evolution
Splicing repression allows the gradual emergence of new Alu-exons in primate evolution
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DOI：
10.7554/elife.19545
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发表时间：
2016-11-18
期刊：
影响因子：
7.7
通讯作者：
Ule, Jernej
中科院分区：
文献类型：
--
作者：
Attig, Jan;Mozos, Igor Ruiz de los;Ule, Jernej
Alu元件是在灵长类进化过程中经常形成新外显子的反转录转座子。在这里，我们评估的相互作用的剪接抑制hnRNPC和无义介导的mRNA衰减（NMD）的质量控制和新的外显子的进化。我们确定了3100个新的外显子，并表明NMD更有效地识别转录与外显子相比，其他外显子提前终止密码子。然而，一些外显子逃脱NMD，特别是当一个相邻的内含子被保留时，突出了剪接和NMD协同抑制的重要性。我们表明3'剪接位点的进化进程与更长的抑制性尿苷束相结合。一旦在古老的外显子3'剪接位点达到一个稳定的阶段，剪接抑制hnRNPC减少，但外显子通常保持敏感的NMD。我们的结论是，压抑图案是最强的下一个神秘的外显子，这些图案的逐渐减弱有助于新的替代外显子的进化出现。
Alu elements are retrotransposons that frequently form new exons during primate evolution. Here, we assess the interplay of splicing repression by hnRNPC and nonsense-mediated mRNA decay (NMD) in the quality control and evolution of new Alu-exons. We identify 3100 new Alu-exons and show that NMD more efficiently recognises transcripts with Alu-exons compared to other exons with premature termination codons. However, some Alu-exons escape NMD, especially when an adjacent intron is retained, highlighting the importance of concerted repression by splicing and NMD. We show that evolutionary progression of 3' splice sites is coupled with longer repressive uridine tracts. Once the 3' splice site at ancient Alu-exons reaches a stable phase, splicing repression by hnRNPC decreases, but the exons generally remain sensitive to NMD. We conclude that repressive motifs are strongest next to cryptic exons and that gradual weakening of these motifs contributes to the evolutionary emergence of new alternative exons.