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Nucleic Acids Res. 2015 Dec 2;43(21):10492-505. doi: 10.1093/nar/gkv956. Epub 2015 Sep 22.

Intergenic Alu exonisation facilitates the evolution of tissue-specific transcript ends.

Author information

1
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.
2
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.
3
Institute of Molecular Biology (IMB) gGmbH, Ackermannweg 4, 55128 Mainz, Germany.
4
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.
5
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.
6
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.
7
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.

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.

PMID:
26400176
PMCID:
PMC4666398
DOI:
10.1093/nar/gkv956
[Indexed for MEDLINE]
Free PMC Article

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