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

• DOI: 10.1101/gr.095273.109
• Publication Date: 2010-01-06T02:10:40Z
• Authors: Michiel J.L. de Hoon; Ryan J. Taft; Takehiro Hashimoto; Mutsumi Kanamori-...; Hideya Kawaji; Mitsuoki Kawano; Mami Kishima; Timo Lassmann; Geoffrey J. Faulkner; John S. Mattick; Carsten O. Daub; Piero Carninci; Jun Kawai; Harukazu Suzuki; Yoshihide Hayashi...
• Keywords: Modulation; 2716 Genetics (clinical); 0303 health sciences; Base Sequence; Sequence Analysis, RNA; Small RNAs; 500; Expression; Genomics; High-Throughput Screening Assays; Mice; MicroRNAs; 03 medical and health sciences; Post transcriptional regulation; 1311 Genetics; Precursor; Animals; Humans; RNA Editing; Sequence Alignment; Biogenesis; Alignment; Gene Library

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.