Fast and effective prediction of microRNA/target duplexes
Open accessAbstract
MicroRNAs (miRNAs) are short RNAs that post-transcriptionally regulate the expression of target genes by binding to the target mRNAs. Although a large number of animal miRNAs has been defined, only a few targets are known. In contrast to plant miRNAs, which usually bind nearly perfectly to their targets, animal miRNAs bind less tightly, with a few nucleotides being unbound, thus producing more complex secondary structures of miRNA/target duplexes. Here, we present a program, RNA-hybrid, that predicts multiple potential binding sites of miRNAs in large target RNAs. In general, the program finds the energetically most favorable hybridization sites of a small RNA in a large RNA. Intramolecular hybridizations, that is, base pairings between target nucleotides or between miRNA nucleotides are not allowed. For large targets, the time complexity of the algorithm is linear in the target length, allowing many long targets to be searched in a short time. Statistical significance of predicted targets is assessed with an extreme value statistics of length normalized minimum free energies, a Poisson approximation of multiple binding sites, and the calculation of effective numbers of orthologous targets in comparative studies of multiple organisms. We applied our method to the prediction of Drosophila miRNA targets in 3′UTRs and coding sequence. RNAhybrid, with its accompanying programs RNAcalibrate and RNAeffective, is available for download and as a Web tool on the Bielefeld Bioinformatics Server ( http://bibiserv.techfak.uni-bielefeld.de/rnahybrid/ ).
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miR-27a/b have multiple putative binding sites in the 3'UTR of human PINK1 mRNA with low binding free energies.
“miR-27a/b have multiple putative binding sites in the 3′UTR of human PINK1 mRNA with low binding free energies (Additional file 2b) [37].”
From miR-27a and miR-27b regulate autophagic clearance of damaged mitochondria by targeting PTEN-induced putative kinase 1 (PINK1) (2016) · cites this paper as [37]
The Introduction and 'Multiple hits per target' section describe RNAhybrid as a method for predicting multiple miRNA binding sites and their free energies. The paper does not report binding sites for miR-27a/b in the human PINK1 3′UTR, so it supports the prediction method but not the specific result attributed here. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRNAhybrid analysis demonstrates extensive pairing between mature miR-181b and a segment on the 5' end of the HMGA1 mRNA.
“While not predicted by Targetscan, RNAhybrid analysis (Rehmsmeier et al., 2004) demonstrates extensive pairing between the mature miR-181b and a segment on the 5’ end of the HMGA1 mRNA.”
From Evidence for miR‐181 involvement in neuroinflammatory responses of astrocytes (2013) · cites this paper as Rehmsmeier et al., 2004
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- Authors
- REHMSMEIER, M., STEFFEN, P., HÖCHSMANN, M., & GIEGERICH, R.
- Affiliations
- Bielefeld University (DE)
- ORCID
- REHMSMEIER, MARC
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2004-09-21
- Volume
- 10
- Issue
- 10
- Pages
- 1507-1517
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC1370637
- OpenAlex
- W2094253263
- Cited by
- 2,560
- References
- 2
- Citations by year
- 2026: 56 · 2025: 114 · 2024: 141 · 2023: 130 · 2022: 156 · 2021: 158 · 2020: 171 · 2019: 150 · 2018: 134 · 2017: 140 · 2016: 141 · 2015: 132 · 2014: 155 · 2013: 141 · 2012: 135
- FWCI
- 21.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PUB – Publications at Bielefeld University (Bielefeld University) (submittedVersion)
- Publikationen an der Universität Bielefeld (Universität Bielefeld) (submittedVersion)
- 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
- miRNA target prediction, RNAhybrid, RNA hybridization, post-transcriptional regulation, 3' untranslated region, RNA secondary structure, minimum free energy, extreme value statistics, Poisson approximation, comparative genomics
- MeSH terms
- Algorithms, Animals, Binding Sites, Drosophila, Nucleic Acid Conformation, RNA Processing, Post-Transcriptional, RNA, Messenger, Thermodynamics, Genes, Insect, Computational Biology, Body Patterning, 3' Untranslated Regions, Databases, Nucleic Acid, MicroRNAs
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