Widespread A-to-I RNA Editing of Alu-Containing mRNAs in the Human Transcriptome

• Published in: PLoS biology Vol. 2; no. 12; p. e391
• Main Authors: Athanasiadis, Alekos, Rich, Alexander, Maas, Stefan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2004; Public Library of Science (PLoS)
• Subjects: 5' Untranslated Regions; Adenosine - chemistry; Adenosine Deaminase - metabolism; Alternative Splicing; Alu Elements; Animals; Base Pair Mismatch; Bioinformatics/Computational Biology; Brain - metabolism; Caenorhabditis elegans; Cell Biology; Computational Biology; Conserved Sequence; Databases, Genetic; DNA, Complementary - metabolism; Exons; Expressed Sequence Tags; Genetics; Genetics/Genomics/Gene Therapy; Genome; Genome, Human; Homo (Human); Humans; Inosine - chemistry; Introns; Kinases; Models, Genetic; Models, Statistical; Molecular Biology/Structural Biology; Molecular Sequence Data; Proteins; Proteome; Receptors, G-Protein-Coupled - metabolism; Ribonucleic acid; RNA; RNA - metabolism; RNA Editing; RNA Processing, Post-Transcriptional; RNA, Messenger - metabolism; Software; Brain; Alternative Splicing; RNA; Exons; RNA Editing; Humans; Databases, Genetic; Molecular Sequence Data; Base Pair Mismatch; Conserved Sequence; Adenosine Deaminase; Expressed Sequence Tags; Adenosine; RNA Processing, Post-Transcriptional; Introns; Computational Biology; Receptors, G-Protein-Coupled; Proteome; Models, Statistical; Caenorhabditis elegans; Animals; 5' Untranslated Regions; Inosine; Models, Genetic; Software; Genome; Genome, Human; Alu Elements; RNA, Messenger; DNA, Complementary
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.0020391

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.