title: Splicing repression allows the gradual emergence of new Alu-exons in primate evolution.
abstract: 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.
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.|MRC-Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Jan
authors.identifier: 0000-0002-2159-2880
authors.initials: J
authors.lastname: Attig
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Igor
authors.identifier: 0000-0003-4097-6422
authors.initials: I
authors.lastname: Ruiz de Los Mozos
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Nejc
authors.initials: N
authors.lastname: Haberman
authors.affiliation: Institute de Biologie de l'ENS (IBENS), CNRS UMR 8197, Paris, France.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.|University College London Genetics Institute, London, United Kingdom.
authors.forename: Warren
authors.initials: W
authors.lastname: Emmett
authors.affiliation: Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt, Frankfurt, Germany.
authors.forename: Kathi
authors.initials: K
authors.lastname: Zarnack
authors.affiliation: Institute of Molecular Biology (IMB), Mainz, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: König
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.|MRC-Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Jernej
authors.identifier: 0000-0002-2452-4277
authors.initials: J
authors.lastname: Ule
mesh_terms: D020087:Alu Elements; D019143:Evolution, Molecular; D005091:Exons; D057809:HEK293 Cells; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000378:metabolism; D006801:Humans; D059365:Nonsense Mediated mRNA Decay; D012326:RNA Splicing
chemical_list: D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C
keywords: Alu elements; evolutionary biology; exon evolution; genomics; human; nonsense mediated mRNA decay; pre-mRNA processing; splicing fidelity