Article abstract
Nature Structural & Molecular Biology 14, 287 - 294 (2007)
Published online: 1 April 2007 | doi:10.1038/nsmb1226
Potent effect of target structure on microRNA function
Dang Long1, Rosalind Lee2, Peter Williams2, Chi Yu Chan1, Victor Ambros2 & Ye Ding1
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that repress protein synthesis by binding to target messenger RNAs. We investigated the effect of target secondary structure on the efficacy of repression by miRNAs. Using structures predicted by the Sfold program, we model the interaction between an miRNA and a target as a two-step hybridization reaction: nucleation at an accessible target site followed by hybrid elongation to disrupt local target secondary structure and form the complete miRNA-target duplex. This model accurately accounts for the sensitivity to repression by let-7 of various mutant forms of the Caenorhabditis eleganslin-41 3' untranslated region and for other experimentally tested miRNA-target interactions in C. elegans and Drosophila melanogaster. These findings indicate a potent effect of target structure on target recognition by miRNAs and establish a structure-based framework for genome-wide identification of animal miRNA targets.
- Wadsworth Center, New York State Department of Health, 150 New Scotland Avenue, Albany, New York 12208, USA.
- Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Correspondence to: Ye Ding1 e-mail: yding@wadsworth.org
Correspondence to: Victor Ambros2 e-mail: vambros@dartmouth.edu
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