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Biochemical principles of miRNA targeting in flies.
Nat Commun.
MicroRNAs direct Argonaute proteins to repress complementary target mRNAs viamRNA degradation or translational inhibition. While mammalian miRNA targeting hasbeen well studied, the principles by which Drosophila miRNAs bind their targetRNAs remain to be fully characterized. Here, we use RNA Bind-n-Seq tosystematically identify binding sites and measure their affinities for fivehighly expressed Drosophila miRNAs. Our results reveal a narrower range ofbinding site diversity in flies compared to mammals, with fly miRNAs favoringcanonical seed-matched sites and exhibiting limited tolerance for imperfectionswithin these sites. We also identified non-canonical site types, includingnucleation-bulged and 3'-only sites, whose binding affinities are comparable tocanonical sites. These findings establish a foundation for future computationalmodels of Drosophila miRNA targeting, enabling predictions of regulatory outcomesin response to cellular signals, and advancing our understanding ofmiRNA-mediated regulation in flies.
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