TY - JOUR TI - Splicing repression allows the gradual emergence of new Alu-exons in primate evolution AU - Attig, Jan AU - Ruiz de los Mozos, Igor AU - Haberman, Nejc AU - Wang, Zhen AU - Emmett, Warren AU - Zarnack, Kathi AU - König, Julian AU - Ule, Jernej A2 - Blencowe, Benjamin J VL - 5 PY - 2016 DA - 2016/11/18 SP - e19545 C1 - eLife 2016;5:e19545 DO - 10.7554/eLife.19545 UR - https://doi.org/10.7554/eLife.19545 AB - 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. KW - pre-mRNA processing KW - Alu elements KW - nonsense mediated mRNA decay KW - exon evolution KW - splicing fidelity JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -