Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome.
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.
Athanasiadis
Alekos
A
Department of Biological Sciences, Lehigh University Bethlehem, Pennsylvania, USA.
Rich
Alexander
A
Maas
Stefan
S
D020121:5' Untranslated Regions; D000241:Adenosine / Q000737:chemistry*; D000243:Adenosine Deaminase / Q000378:metabolism; D017398:Alternative Splicing; D020087:Alu Elements; D000818:Animals; D020137:Base Pair Mismatch; D001921:Brain / Q000378:metabolism; D017173:Caenorhabditis elegans; D019295:Computational Biology; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000378:metabolism; D030541:Databases, Genetic; D005091:Exons; D020224:Expressed Sequence Tags; D016678:Genome; D015894:Genome, Human; D006801:Humans; D007288:Inosine / Q000737:chemistry*; D007438:Introns; D008957:Models, Genetic; D015233:Models, Statistical; D008969:Molecular Sequence Data; D020543:Proteome; D012313:RNA / Q000378:metabolism; D017393:RNA Editing; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012984:Software
D020121:5' Untranslated Regions; D018076:DNA, Complementary; D020543:Proteome; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D007288:Inosine; D012313:RNA; D000243:Adenosine Deaminase; D000241:Adenosine