widespread a-to-i rna editing of alu-containing mrnas in the human transcriptome广泛a-to-i rna编辑alu-containing mrna在人类转录组.pdf

Open access, freely available online PLoS BIOLOGY Widespread A-to-I RNA Editing of Alu-Containing mRNAs in the Human Transcriptome 1,2 2 1* Alekos Athanasiadis , Alexander Rich , Stefan Maas 1 Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of America, 2 Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America 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