Complementary miRNA pairs suggest a regulatory role for miRNA:miRNA duplexes - PubMed (original) (raw)

Complementary miRNA pairs suggest a regulatory role for miRNA:miRNA duplexes

Eric C Lai et al. RNA. 2004 Feb.

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.

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Figures

FIGURE 1.

FIGURE 1.

Subsets of Drosophila miRNAs are highly complementary to each other. (A) Alignment of the K box-related pre-miRNA sequences for mir-5, mir-6-1, mir-6-2, and mir-6-3; the K box-complementary signature (UAUCACAG) is boxed. The nucleotides in bold indicate the mature miRNAs; thus, miR-5 derives from the left arm of its precursor and miR-6 from the right arms of the three mir-6 genes. Shaded regions highlight similarity between mature miRNAs and corresponding miRNA* regions, with the miR-5-similar region in light red and the miR-6-similar region in dark red. (B) Proposed miR-5:miR-6 duplex. As the three mir-6 genes produce identical miRNAs, only one alignment is shown. miR-5 also shows complementarity to other members of the K-box miRNA family, albeit to a lesser extent (data not shown). (C) The mir-5 and mir-6 genes reside in a gene cluster containing other non-K-box family miRNAs; these include the Brd-box family gene mir-4 and two others that form their own subfamily, miR-309 and miR-3 (shaded black). (D) Alignment of Brd box-related miRNAs. Mature miRNAs are in bold; the Brd box-complementary signature (UAAAGCU) is boxed. Blue shading highlights similarity between mature miRNAs and corresponding miRNA* regions, with miR-9-similar sequences in light blue and miR-4/miR-79-similar sequences in dark blue. (E) Examples of miRNA complements among the set of Brd box-related miRNAs. Comparison with the miR-4:miR-4* duplex shows that miR-4 is more complementary to miR-9a than to its own miRNA* species. (F) Complementary Brd box-related miRNAs reside in a gene complex with one unrelated miRNA (mir-306); mir-9a and mir-4 are located elsewhere in the genome. (G) Mammalian miR-9 and miR-131, members of the Brd box-related family, potentially derive from the same pre-miRNAs; chromosome positions are for the human loci. (H) Proposed miR-9:miR-131 duplex.

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