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Genome Res. 2010 Feb;20(2):257-64. doi: 10.1101/gr.095273.109. Epub 2010 Jan 5.

Cross-mapping and the identification of editing sites in mature microRNAs in high-throughput sequencing libraries.

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Omics Science Center, RIKEN Yokohama Institute, Tsurumi, Yokohama 230-0045, Japan.


MicroRNAs (miRNAs) are short (20-23 nt) RNAs that are sequence-specific mediators of transcriptional and post-transcriptional regulation of gene expression. Modern high-throughput technologies enable deep sequencing of such RNA species on an unprecedented scale. We find that the analysis of small RNA deep-sequencing libraries can be affected by cross-mapping, in which RNA sequences originating from one locus are inadvertently mapped to another. Similar to cross-hybridization on microarrays, cross-mapping is prevalent among miRNAs, as they tend to occur in families, are similar or derived from repeat or structural RNAs, or are post-transcriptionally modified. Here, we develop a strategy to correct for cross-mapping, and apply it to the analysis of RNA editing in mature miRNAs. In contrast to previous reports, our analysis suggests that RNA editing in mature miRNAs is rare in animals.

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