Widespread RNA Editing of Embedded Alu Elements in the Human Transcriptome

  1. Dennis D.Y. Kim1,
  2. Thomas T.Y. Kim2,
  3. Thomas Walsh3,
  4. Yoshifumi Kobayashi1,
  5. Tara C. Matise4,
  6. Steven Buyske4,5, and
  7. Abram Gabriel1,6
  1. 1 Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA
  2. 2 Department of Computer Science, Rutgers University, Piscataway, New Jersey 08854, USA
  3. 3 Graduate Program in Computer Science, Rutgers University, Piscataway, New Jersey 08854, USA
  4. 4 Department of Genetics, Rutgers University, Piscataway, New Jersey 08854, USA
  5. 5 Department of Statistics, Rutgers University, Piscataway, New Jersey 08854, USA

Abstract

More than one million copies of the ∼300-bp Alu element are interspersed throughout the human genome, with up to 75% of all known genes having Alu insertions within their introns and/or UTRs. Transcribed Alu sequences can alter splicing patterns by generating new exons, but other impacts of intragenic Alu elements on their host RNA are largely unexplored. Recently, repeat elements present in the introns or 3′-UTRs of 15 human brain RNAs have been shown to be targets for multiple adenosine to inosine (A-to-I) editing. Using a statistical approach, we find that editing of transcripts with embedded Alu sequences is a global phenomenon in the human transcriptome, observed in 2674 (∼2%) of all publicly available full-length human cDNAs (n = 128,406), from >250 libraries and >30 tissue sources. In the vast majority of edited RNAs, A-to-I substitutions are clustered within transcribed sense or antisense Alu sequences. Edited bases are primarily associated with retained introns, extended UTRs, or with transcripts that have no corresponding known gene. Therefore, Alu-associated RNA editing may be a mechanism for marking nonstandard transcripts, not destined for translation.

Footnotes

  • [Supplemental material is available online at www.genome.org.]

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.2855504.

  • 6 Corresponding author. E-MAIL gabriel{at}cabm.rutgers.edu; FAX (732) 235-4880.

    • Accepted July 9, 2004.
    • Received June 4, 2004.
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