Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Hum Mol Genet. 2009 Dec 15;18(24):4801-7. doi: 10.1093/hmg/ddp443. Epub 2009 Sep 23.

Adenosine deamination in human transcripts generates novel microRNA binding sites.

Author information

  • 1Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA.

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.

PMID:
19776031
[PubMed - indexed for MEDLINE]
PMCID:
PMC2778373
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk