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An alternative mode of microRNA target recognition
Open accessAbstract
MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (positions 2-7). Recently, a precise genome-wide map of miRNA interaction sites in mouse brain was generated by high-throughput sequencing and analysis of clusters of ~50-nucleotide mRNA tags cross-linked to Argonaute (Ago HITS-CLIP). By analyzing Ago HITS-CLIP 'orphan clusters'-Ago binding regions from HITS-CLIP that cannot be explained by canonical seed matches-we have now identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (positions 5-6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise ≥15% of all Ago-miRNA interactions in mouse brain and are evolutionarily conserved. We call position 6 the 'pivot' nucleotide and suggest a model in which a transitional 'nucleation bulge' leads to functional bulge mRNA-miRNA interactions, expanding the number of potential miRNA regulatory sites.
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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 [140]
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Metadata
- Authors
- Chi, S. W., Hannon, G. J., & Darnell, R. B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Chi, Sung Wook
- Darnell, Robert B
- Venue
- Nature Structural & Molecular Biology
- Published
- 2012-02-12
- Volume
- 19
- Issue
- 3
- Pages
- 321-327
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC3541676
- OpenAlex
- W2167754184
- Cited by
- 328
- References
- 46
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 7 · 2023: 5 · 2022: 13 · 2021: 21 · 2020: 14 · 2019: 21 · 2018: 25 · 2017: 27 · 2016: 34 · 2015: 41 · 2014: 45 · 2013: 38 · 2012: 31
- FWCI
- 16.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5p30ca045508-35)
- National Cancer Institute (P30-CA045508, P01CA013106)
- National Institute of General Medical Sciences (R01GM062534)
- National Institute of Neurological Disorders and Stroke (R01NS034389)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- miR-124, Argonaute proteins, HITS-CLIP, miRNA-mRNA interactions, mouse brain
- MeSH terms
- Binding Sites, HeLa Cells, Humans, Models, Genetic, Base Pairing, MicroRNAs
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