Combinatorial microRNA target predictions
Abstract
MicroRNAs are small noncoding RNAs that recognize and bind to partially complementary sites in the 3' untranslated regions of target genes in animals and, by unknown mechanisms, regulate protein production of the target transcript. Different combinations of microRNAs are expressed in different cell types and may coordinately regulate cell-specific target genes. Here, we present PicTar, a computational method for identifying common targets of microRNAs. Statistical tests using genome-wide alignments of eight vertebrate genomes, PicTar's ability to specifically recover published microRNA targets, and experimental validation of seven predicted targets suggest that PicTar has an excellent success rate in predicting targets for single microRNAs and for combinations of microRNAs. We find that vertebrate microRNAs target, on average, roughly 200 transcripts each. Furthermore, our results suggest widespread coordinate control executed by microRNAs. In particular, we experimentally validate common regulation of Mtpn by miR-375, miR-124 and let-7b and thus provide evidence for coordinate microRNA control in mammals.
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STAT3 is negatively regulated by miR-21 according to the microarray data and is a predicted miR-21 target.
“STAT3, the other gene that may play a tumor suppressor function in GBM (11), is also negatively regulated by miR-21 according to the microarray data (see Table S1 in the supplemental material) and is a predicted miR-21 target (29, 34).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [29]
A single microRNA can target numerous mRNAs, and a single mRNA can be targeted by numerous microRNAs.
“however, a single microRNA can target numerous mRNAs, and a single mRNA can be targeted by numerous microRNAs [10].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [10]
Various algorithms have been developed to predict miRNA:mRNA interactions throughout the transcriptome based on sequence complementarity.
“Building upon this principle of sequence complementarity, various algorithms have been developed to predict miRNA:mRNA interactions throughout the transcriptome (Agarwal et al., 2015;Krek et al., 2005).”
From Scalable and deep profiling of mRNA targets for individual microRNAs with chimeric eCLIP (2022) · cites this paper as Krek et al., 2005
Luciferase reporter assays have identified myotrophin (Mtpn) as a target of miR-124 regulation, both of which are highly expressed in neurons throughout the brain.
“Additionally, luciferase reporter assays have identi-fied myotrophin (Mtpn) as a target of miR-124 regulation (Krek et al. 2005), both of which are highly expressed in neurons throughout the brain (Fujigasaki et al. 1996).”
From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Krek et al. 2005
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“To identify whether the 3’ UTR variant in Rfx1 (c.*935G>A) was located in a miRNA binding site, the online tools PicTar [25] (https://pictar.mdc-berlin.de/, Accessed on 05/26/2020) and miRDB [24] (http://mirdb.org/, Accessed on 05/26/2020) were used.”
MethodInfluential
- Authors
- Krek, A., Grün, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I., Gunsalus, K. C., Stoffel, M., & Rajewsky, N.
- Affiliations
- New York University (US)
- Rockefeller University (US)
- Corresponding author
- Rajewsky, Nikolaus
- Venue
- Nature Genetics
- Published
- 2005-04-03
- Volume
- 37
- Issue
- 5
- Pages
- 495-500
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2050869737
- Cited by
- 4,603
- References
- 0
- Citations by year
- 2026: 33 · 2025: 52 · 2024: 88 · 2023: 106 · 2022: 124 · 2021: 149 · 2020: 161 · 2019: 175 · 2018: 215 · 2017: 253 · 2016: 285 · 2015: 320 · 2014: 373 · 2013: 363 · 2012: 355
- FWCI
- 66.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Francis Crick Institute
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- miRNA target prediction, 3' untranslated region, coordinate gene regulation, miR-375, miR-124, let-7b, non-coding RNA
- MeSH terms
- Algorithms, Animals, Computational Biology, MicroRNAs
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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.
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