NDLI: Adenosine deamination in human transcripts generates novel microRNA binding sites

Content Provider	PubMed Central
Author	Borchert, Glen M. Gilmore, Brian L. Spengler, Ryan M. Xing, Yi Lanier, William Bhattacharya, Debashish Davidson, Beverly L.
Abstract	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.
Related Links	http://dx.doi.org/10.1093/hmg/ddp443
Ending Page	4807
Page Count	7
Starting Page	4801
File Format	PDF
ISSN	09646906
e-ISSN	14602083
Journal	Human Molecular Genetics
Issue Number	24
Volume Number	18
Language	English
Publisher	Oxford University Press
Publisher Date	2009-12-15
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Genetics(clinical) Genetics Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Genetics (clinical)

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