title: Intergenic Alu exonisation facilitates the evolution of tissue-specific transcript ends.
abstract: The 3' untranslated regions (3' UTRs) of transcripts serve as important hubs for posttranscriptional gene expression regulation. Here, we find that the exonisation of intergenic Alu elements introduced new terminal exons and polyadenylation sites during human genome evolution. While Alu exonisation from introns has been described previously, we shed light on a novel mechanism to create alternative 3' UTRs, thereby opening opportunities for differential posttranscriptional regulation. On the mechanistic level, we show that intergenic Alu exonisation can compete both with alternative splicing and polyadenylation in the upstream gene. Notably, the Alu-derived isoforms are often expressed in a tissue-specific manner, and the Alu-derived 3' UTRs can alter mRNA stability. In summary, we demonstrate that intergenic elements can affect processing of preceding genes, and elucidate how intergenic Alu exonisation can contribute to tissue-specific posttranscriptional regulation by expanding the repertoire of 3' UTRs.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK International Centre for Genetic Engineering and Biotechnology, Padriciano 99, 34149 Trieste, Italy.
authors.forename: Mojca
authors.initials: M
authors.lastname: Tajnik
authors.affiliation: UCL Genetics Institute, Department of Genetics, Evolution & Environment, University College London, Gower Street, London WC1E 6BT, UK Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vigilante
authors.affiliation: Institute of Molecular Biology (IMB) gGmbH, Ackermannweg 4, 55128 Mainz, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Braun
authors.affiliation: Institute of Molecular Biology (IMB) gGmbH, Ackermannweg 4, 55128 Mainz, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Hänel
authors.affiliation: UCL Genetics Institute, Department of Genetics, Evolution & Environment, University College London, Gower Street, London WC1E 6BT, UK Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK Okinawa Institute of Science & Technology, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa 904-0495, Japan.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Luscombe
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Jernej
authors.initials: J
authors.lastname: Ule
authors.affiliation: Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK Buchmann Institute for Molecular Life Sciences (BMLS), Max-von-Laue-Str. 15, 60438 Frankfurt, Germany kathi.zarnack@bmls.de.
authors.forename: Kathi
authors.initials: K
authors.lastname: Zarnack
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK Institute of Molecular Biology (IMB) gGmbH, Ackermannweg 4, 55128 Mainz, Germany Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK j.koenig@imb-mainz.de.
authors.forename: Julian
authors.initials: J
authors.lastname: König
mesh_terms: D020413:3' Untranslated Regions; D020087:Alu Elements; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D021901:DNA, Intergenic / Q000737:chemistry; D019143:Evolution, Molecular; D005091:Exons; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000378:metabolism; D006801:Humans; D007438:Introns; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D026723:Polyadenylation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012326:RNA Splicing; D012261:Ribonucleoproteins / Q000378:metabolism; D000072668:Splicing Factor U2AF
chemical_list: D020413:3' Untranslated Regions; D021901:DNA, Intergenic; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C000607494:U2AF2 protein, human; D012313:RNA; D004247:DNA