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

RNA. 2004 Feb;10(2):171-5. doi: 10.1261/rna.5191904.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / genetics
  • Drosophila / physiology
  • Evolution, Molecular
  • Gene Expression Regulation / physiology*
  • MicroRNAs / physiology*
  • Monte Carlo Method
  • RNA, Double-Stranded / physiology*


  • MicroRNAs
  • RNA, Double-Stranded