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

Hervé Seitz12*, Jogender S Tushir3 and Phillip D Zamore3*

Author Affiliations

1 Laboratoire de Biologie Moléculaire Eucaryote, 118 route de Narbonne, Université Toulouse III Paul Sabatier (UPS), F-31000 Toulouse, France

2 Laboratoire de Biologie Moléculaire Eucaryote, 118 route de Narbonne, Centre national de la recherche scientifique (CNRS), F-31000 Toulouse, France

3 Howard Hughes Medical Institute and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation street, Worcester, MA 01605, USA

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Silence 2011, 2:4  doi:10.1186/1758-907X-2-4

Published: 7 June 2011



MicroRNA (miRNA) are diverse in sequence and have a single known sequence bias: they tend to start with uridine (U).


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*.


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.