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Citation
Kertesz, M., Iovino, N., Unnerstall, U., Gaul, U., Segal, E. (2007). The role of site accessibility in microRNA target recognition.  Nat. Genet. 39(10): 1278--1284.
FlyBase ID
FBrf0216115
Publication Type
Research paper
Abstract

MicroRNAs are key regulators of gene expression, but the precise mechanisms underlying their interaction with their mRNA targets are still poorly understood. Here, we systematically investigate the role of target-site accessibility, as determined by base-pairing interactions within the mRNA, in microRNA target recognition. We experimentally show that mutations diminishing target accessibility substantially reduce microRNA-mediated translational repression, with effects comparable to those of mutations that disrupt sequence complementarity. We devise a parameter-free model for microRNA-target interaction that computes the difference between the free energy gained from the formation of the microRNA-target duplex and the energetic cost of unpairing the target to make it accessible to the microRNA. This model explains the variability in our experiments, predicts validated targets more accurately than existing algorithms, and shows that genomes accommodate site accessibility by preferentially positioning targets in highly accessible regions. Our study thus demonstrates that target accessibility is a critical factor in microRNA function.

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Genet.
    Title
    Nature Genetics
    Publication Year
    1992-
    ISBN/ISSN
    1061-4036 1546-1718
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