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. 2006;7(4):R27.
doi: 10.1186/gb-2006-7-4-r27. Epub 2006 Apr 4.

RNA editing of human microRNAs

Matthew J Blow  1 , Russell J Grocock, Stijn van Dongen, Anton J Enright, Ed Dicks, P Andrew Futreal, Richard Wooster, Michael R Stratton
Affiliations

RNA editing of human microRNAs

Matthew J Blow et al. Genome Biol. 2006.

Abstract

Background: MicroRNAs (miRNAs) are short RNAs of around 22 nucleotides that regulate gene expression. The primary transcripts of miRNAs contain double-stranded RNA and are therefore potential substrates for adenosine to inosine (A-to-I) RNA editing.

Results: We have conducted a survey of RNA editing of miRNAs from ten human tissues by sequence comparison of PCR products derived from matched genomic DNA and total cDNA from the same individual. Six out of 99 (6%) miRNA transcripts from which data were obtained were subject to A-to-I editing in at least one tissue. Four out of seven edited adenosines were in the mature miRNA and were predicted to change the target sites in 3' untranslated regions. For a further six miRNAs, we identified A-to-I editing of transcripts derived from the opposite strand of the genome to the annotated miRNA. These miRNAs may have been annotated to the wrong genomic strand.

Conclusion: Our results indicate that RNA editing increases the diversity of miRNAs and their targets, and hence may modulate miRNA function.

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Figures

Figure 1
Figure 1
A-to-I RNA editing of miRNA precursors in human tissues. The extent of A-to-I editing at each editing site is indicated by the color scale. Each colored box represents the average extent of editing calculated from at least two PCR product sequences, at least one of which was sequenced in both directions. Gray boxes indicate miRNAs that could not be amplified. The number in brackets after the miRNA name is the position of the edited adenosine from the 5' end of the pre-miRNA or equivalent antisense pre-miRNA from the miRNA registry.
Figure 2
Figure 2
Positions of edited adenosines in human pri-miRNAs and antisense pri-miRNAs. Folded pri-miRNA structures were taken from the miRNA registry [6]. Antisense pre-miRNA structures were generated from the reverse complement pri-miRNA sequence using MFOLD [38]. Mature miRNA sequences of around 22 nucleotides and antisense mature miRNA sequences of around 22 nucleotides are indicated by red letters. Edited adenosines are highlighted in yellow. In antisense Hsa-mir-371, edited adenosines were found to reside in base-paired sequence extending beyond the annotated hairpin. Additional bases are in gray.
Figure 3
Figure 3
GO term comparison of edited and unedited miRNA target predictions. For each edited miRNA, GO terms from level 4 of the 'biological process' category that are over-represented in predicted targets of the unedited or edited miRNA (indicated by +) compared with all Ensembl genes were identified. All values are normalized and colored in terms of significance, with bright red cells indicating that a miRNA specifically targets genes in that GO functional class.
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