Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome

PLoS Biol. 2004 Dec;2(12):e391. doi: 10.1371/journal.pbio.0020391. Epub 2004 Nov 9.


RNA editing by adenosine deamination generates RNA and protein diversity through the posttranscriptional modification of single nucleotides in RNA sequences. Few mammalian A-to-I edited genes have been identified despite evidence that many more should exist. Here we identify intramolecular pairs of Alu elements as a major target for editing in the human transcriptome. An experimental demonstration in 43 genes was extended by a broader computational analysis of more than 100,000 human mRNAs. We find that 1,445 human mRNAs (1.4%) are subject to RNA editing at more than 14,500 sites, and our data further suggest that the vast majority of pre-mRNAs (greater than 85%) are targeted in introns by the editing machinery. The editing levels of Alu-containing mRNAs correlate with distance and homology between inverted repeats and vary in different tissues. Alu-mediated RNA duplexes targeted by RNA editing are formed intramolecularly, whereas editing due to intermolecular base-pairing appears to be negligible. We present evidence that these editing events can lead to the posttranscriptional creation or elimination of splice signals affecting alternatively spliced Alu-derived exons. The analysis suggests that modification of repetitive elements is a predominant activity for RNA editing with significant implications for cellular gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Adenosine / chemistry*
  • Adenosine Deaminase / metabolism
  • Alternative Splicing
  • Alu Elements*
  • Animals
  • Base Pair Mismatch
  • Brain / metabolism
  • Caenorhabditis elegans
  • Computational Biology
  • Conserved Sequence
  • DNA, Complementary / metabolism
  • Databases, Genetic
  • Exons
  • Expressed Sequence Tags
  • Genome
  • Genome, Human
  • Humans
  • Inosine / chemistry*
  • Introns
  • Models, Genetic
  • Models, Statistical
  • Molecular Sequence Data
  • Proteome
  • RNA / metabolism
  • RNA Editing*
  • RNA Processing, Post-Transcriptional
  • RNA, Messenger / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Software


  • 5' Untranslated Regions
  • DNA, Complementary
  • Proteome
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Inosine
  • RNA
  • Adenosine Deaminase
  • Adenosine

Associated data

  • GENBANK/AB007969
  • GENBANK/AB037838
  • GENBANK/AB040930
  • GENBANK/AB046844
  • GENBANK/AB095924
  • GENBANK/AK021666
  • GENBANK/AK055562
  • GENBANK/AK092837
  • GENBANK/AK094425
  • GENBANK/BC039501