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The regulatory activity of microRNA(*) species has substantial influence on microRNA and 3' UTR evolution.

by: Katsutomo Okamura, Michael D D Phillips, David M M Tyler, Hong Duan, Yu-Ting T Chou, Eric C C Lai
Nature structural & molecular biology (30 March 2008)


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During microRNA (miRNA) biogenesis, one strand of a approximately 21-22-nucleotide RNA duplex is preferentially selected for entry into a silencing complex. The other strand, known as the miRNA(*) species, has typically been assumed to be a carrier strand. Here we show that, although Drosophila melanogaster miRNA(*) species are less abundant than their partners, they are often present at physiologically relevant levels and can associate with Argonaute proteins. Comparative genomic analyses revealed that >40% of miRNA(*) sequences resist nucleotide divergence across Drosophilid evolution, and at least half of these well-conserved miRNA(*) species select for conserved 3' untranslated region seed matches well above background noise. Finally, we validated the inhibitory activity of miRNA(*) species in both cultured cells and transgenic animals. These data broaden the reach of the miRNA regulatory network and suggest an important mechanism that diversifies miRNA function during evolution.


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