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The role of site accessibility in microRNA target recognition
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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“current target prediction algorithms often identify many false positive target genes and there is no strong overlap in the predicted target gene list among prediction algorithms [138-141].”
From MicroRNAs in brain cholesterol metabolism and their implications for Alzheimer's disease (2016) · cites this paper as [139]
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Metadata
- 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
- Venue
- Nature Genetics
- Published
- 2007-09-23
- Volume
- 39
- Issue
- 10
- Pages
- 1278-1284
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- 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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