Eric C. Lai, Colin Wiel, and Gerald M. Rubin
Howard Hughes Medical Institute, University of California, Berkeley, Department of Molecular and Cell Biology, Berkeley, California 94720-3200, USA
Reprint requests to: Eric Lai, H. Hughes Medical Inst., Univ. of
Calif., Berkeley, Dept. of Molecular and Cell Biology, 545 Life Sciences
Addition, Berkeley, CA 94720-3200, USA;
e-mail: lai@fruitfly.org
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.
Keywords: microRNA; miRNA; miRNA*; RNA duplex
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2. Lai E, "RNA Sensors and Riboswitches: Self-Regulating Messages".
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