Human Molecular Genetics Advance Access originally published online on September 23, 2009
Human Molecular Genetics 2009 18(24):4801-4807; doi:10.1093/hmg/ddp443
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Adenosine deamination in human transcripts generates novel microRNA binding sites
1 Department of Internal Medicine, 2 Genetics Training Program, 3 Molecular and Cellular Biology Training Program, 4 Department of Biomedical Engineering, 5 Department of Biological Sciences, 6 Department of Neurology and 7 Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA
* To whom correspondence should be addressed at: Department of Internal Medicine, University of Iowa, 200 EMRB, Iowa City, IA 52242, USA. Tel: +1 3193535511; Fax: +1 3193535572; Email: beverly-davidson{at}uiowa.edu
Received July 21, 2009; Accepted September 21, 2009
Animals regulate gene expression at multiple levels, contributing to the complexity of the proteome. Among these regulatory events are post-transcriptional gene silencing, mediated by small non-coding RNAs (e.g. microRNAs), and adenosine-to-inosine (A-to-I) editing, generated by adenosine deaminases that act on double-stranded RNA (ADAR). Recent data suggest that these regulatory processes are connected at a fundamental level. A-to-I editing can affect Drosha processing or directly alter the microRNA (miRNA) sequences responsible for mRNA targeting. Here, we analyzed the previously reported adenosine deaminations occurring in human cDNAs, and asked if there was a relationship between A-to-I editing events in the mRNA 3' untranslated regions (UTRs) and mRNA:miRNA binding. We find significant correlations between A-to-I editing and changes in miRNA complementarities. In all, over 3000 of the 12 723 distinct adenosine deaminations assessed were found to form 7-mer complementarities (known as seed matches) to a subset of human miRNAs. In 200 of the ESTs, we also noted editing within a specific 13 nucleotide motif. Strikingly, deamination of this motif simultaneously creates seed matches to three (otherwise unrelated) miRNAs. Our results suggest the creation of miRNA regulatory sites as a novel function for ADAR activity. Consequently, many miRNA target sites may only be identifiable through examining expressed sequences.
Present address: School of Biological Sciences, Illinois State University, Normal, IL 61790.
Present address: Department of Ecology, Evolution and Natural Resources, Rutgers University, New Brunswick, NJ 08901 USA.