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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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