Cited by 2,460MicroRNA in disease regulationRNA and protein synthesis mechanismsRNA Research and Splicing

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The role of site accessibility in microRNA target recognition

Kertesz, Michael, Iovino, Nicola, Unnerstall, Ulrich, Gaul, Ulrike, Segal, Eran·2007·Nature Genetics

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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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Self-citation
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Authors: Kertesz, M., Iovino, N., Unnerstall, U., Gaul, U., & Segal, E.
Affiliations: Weizmann Institute of Science (IL)
Rockefeller University (US)
Corresponding author: Gaul, Ulrike
Segal, Eran
ORCID: Iovino, Nicola
Gaul, Ulrike
Segal, Eran
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2007-09-23
Volume: 39
Issue: 10
Pages: 1278-1284
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng2135
OpenAlex: W2149785901
Cited by: 2,460
References: 38
Citations by year: 2026: 46 · 2025: 66 · 2024: 76 · 2023: 89 · 2022: 118 · 2021: 133 · 2020: 143 · 2019: 141 · 2018: 159 · 2017: 155 · 2016: 171 · 2015: 181 · 2014: 194 · 2013: 189 · 2012: 185
FWCI: 33.14
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords: microRNA, protein synthesis inhibition, base pairing, free energy model, miRNA target prediction, mRNA secondary structure, sequence complementarity
MeSH terms: Animals, Binding Sites, Drosophila, Humans, Models, Biological, Nucleic Acid Conformation, RNA, Messenger, Thermodynamics, Caenorhabditis elegans, MicroRNAs, Mice

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