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MicroRNAs (miRNAs) modulate transcript stability and translation. Functional mature miRNAs are processed from one or both arms of the hairpin precursor. The miR‐100/10 family has undergone three independent evolutionary events that have switched the arm from which the functional miRNA is processed. The dominant miR‐10 sequences in the insects  Drosophila melanogaster  and  Tribolium castaneum  are processed from opposite arms. However, the duplex produced by Dicer cleavage has an identical sequence in fly and beetle. Expression of the  Tribolium  miR‐10 sequence in  Drosophila  S2 cells recapitulates the native beetle pattern. Thus, arm usage is encoded in the primary miRNA sequence, but outside the mature miRNA duplex. We show that the predicted messenger RNA targets and inferred function of sequences from opposite arms differ significantly. Arm switching is likely to be general, and provides a fundamental mechanism to evolve the function of a miRNA locus and target gene network.

MicroRNA evolution by arm switching