A 5′-uridine amplifies miRNA/miRNA* asymmetry in Drosophila by promoting RNA-induced silencing complex formation
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
Silence 2011, 2:4 doi:10.1186/1758-907X-2-4Published: 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.