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Background  MicroRNA (miRNA) are diverse in sequence and have a single known sequence bias: they tend to start with uridine (U).    Results  Our analyses of fly, worm and mouse miRNA sequence data reveal that the 5′-U is recognized after miRNA production. Only one of the two strands can be assembled into Argonaute protein from a single miRNA/miRNA* molecule: in fly embryo lysate, a 5′-U promotes miRNA loading while decreasing the loading of the miRNA*.    Conclusion  We suggest that recognition of the 5′-U enhances Argonaute loading by a mechanism distinct from its contribution to weakening base pairing at the 5′-end of the prospective miRNA and, as recently proposed in  Arabidopsis  and in humans, that it improves miRNA precision by excluding incorrectly processed molecules bearing other 5′-nt.

A 5′-uridine amplifies miRNA/miRNA* asymmetry in Drosophila by promoting RNA-induced silencing complex formation