title: Complementary miRNA pairs suggest a regulatory role for miRNA:miRNA duplexes.
abstract: microRNAs (miRNAs) are 21-22-nucleotide noncoding RNAs that are widely believed to regulate complementary mRNA targets. However, due to the modest amount of pairing involved, only a few out of the hundreds of known animal miRNAs have thus far been connected to mRNA targets. Here, we considered the possibility that miRNAs might regulate non-mRNA targets, namely other miRNAs. To do so, we conducted a systematic assessment of the nearly complete catalogs of animal miRNAs for potential miRNA:miRNA complements. Our analysis uncovered several compelling examples that strongly suggest a function for miRNA duplexes, thus adding a potential layer of regulatory sophistication to the small RNA world. Interestingly, the most striking examples involve miRNAs complementary to members of the K-box family and Brd-box family, two classes of miRNAs previously implicated in regulation of Notch target genes. We emphasize that patterns of nucleotide constraint indicate that miRNA complementarity is not a simple consequence of miRNA:miRNA* complementarity; however, our findings do suggest that the potential regulatory consequences of the latter also deserve investigation.
authors.affiliation: Howard Hughes Medical Institute, University of California, Berkeley, Department of Molecular and Cell Biology, Berkeley, California 94720-3200, USA. lai@fruitfly.org
authors.forename: Eric C
authors.initials: EC
authors.lastname: Lai
authors.forename: Colin
authors.initials: C
authors.lastname: Wiel
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rubin
mesh_terms: D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000502:physiology; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D009010:Monte Carlo Method; D012330:RNA, Double-Stranded / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D012330:RNA, Double-Stranded