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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions*
  • Alu Elements*
  • Cell Line
  • DNA / metabolism
  • DNA, Intergenic / chemistry
  • Evolution, Molecular*
  • Exons*
  • Heterogeneous-Nuclear Ribonucleoprotein Group C / metabolism
  • Humans
  • Introns
  • Nuclear Proteins / metabolism
  • Organ Specificity
  • Polyadenylation
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA / metabolism
  • RNA Splicing
  • Ribonucleoproteins / metabolism
  • Splicing Factor U2AF


  • 3' Untranslated Regions
  • DNA, Intergenic
  • Heterogeneous-Nuclear Ribonucleoprotein Group C
  • Nuclear Proteins
  • Protein Isoforms
  • Ribonucleoproteins
  • Splicing Factor U2AF
  • U2AF2 protein, human
  • RNA
  • DNA