Splicing repression allows the gradual emergence of new Alu-exons in primate evolution

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 alte...Alu元件（Alu elements）是一类在灵长类演化过程中频繁形成新外显子的逆转录转座子。本研究旨在剖析异质性核核糖核蛋白C（hnRNPC）介导的剪接抑制与无义介导的mRNA降解（NMD）之间的互作关系，及其在新型Alu外显子的质量控制与演化进程中的调控功能。我们共鉴定出3100个新型Alu外显子，并证实相较于其他携带提前终止密码子的外显子，NMD对携带Alu外显子的转录本识别效率更为显著。然而，部分Alu外显子可逃逸NMD的监控，这种情况在相邻内含子发生滞留时尤为常见，这凸显了剪接抑制与NMD协同调控的关键意义。研究表明，3'剪接位点的演化进程与更长的抑制性尿苷序列段呈耦合关联。当古老Alu外显子的3'剪接位点进入稳定阶段后，hnRNPC介导的剪接抑制作用会有所减弱，但此类外显子通常仍对NMD敏感。我们最终得出结论：抑制基序在隐蔽外显子旁侧的作用强度最高，且此类基序的逐步弱化推动了新型……