Hunting the Needle in the Haystack: A Guide to Obtain Biologically Meaningful MicroRNA Targets
Abstract
:1. Introduction
2. Identification of Putative Direct MicroRNAs (miRNAs)–mRNA Interactions of Interest
2.1. Bioinformatic Tools Predicting Direct miRNA–mRNA Interactions in Mammals
Prediction Tool | Criteria for Prediction and Ranking | Last Update | Output Formats | Available Downloads |
---|---|---|---|---|
TargetScan [45] | stringent seed: seed match pairing, number of target sites, free folding energy of miRNA—target site interactions, target site evolutionary conservation, target site context and accessibility | 2012 | table of miRNA-target interactions, image of 3' UTR with miRNA binding sites, alignment of orthologous 3' UTRs | all target site predictions, algorithms (Perl scripts) |
PicTar [46] | stringent seed: seed match pairing, number of target sites, target site evolutionary conservation, predicted optimal free energy of target sites | 2007 | table of miRNA-target interactions, alignment of orthologous 3' UTRs | all target site predictions |
ElMMo [47] | stringent seed: seed match pairing, number of target sites, target site evolutionary conservation | 2009 | table of miRNA-target interactions, listing of evolutionarily conserved seed matches | all target site predictions |
MirTarget2 [48] | stringent seed: seed match pairing, seed match evolutionary conservation, target site base composition, free energy of target site, target site location | 2012 | table of miRNA-target interactions, 3' UTR sequence with seed matches highlighted | all target site predictions |
PITA [49] | seed: seed match paring (G:U wobble base pairs allowed), number of target sites, free folding energy of miRNA—target site interactions and energy cost of 3' UTR secondary structure unfolding | 2008 | Excel spreadsheets containing miRNA-target interactions for distinct target sites or entire 3' UTRs | all target site predictions, algorithms (Perl scripts) |
Miranda [50] | seed : seed match paring (G:U wobble base pairs allowed), number of target sites, target site evolutionary conservation, free energy of miRNA-target duplex | 2010 | table of miRNA-3' UTR interactions, miRNA-target site alignment | all target site predictions, algorithms (C) |
DIANA-microT [51] | seed : seed match paring (G:U wobble base pairs allowed), target site evolutionary conservation | 2012 | table of miRNA-target interactions, miRNA-target site alignment | all target site predictions |
rna22 [52] | seed : seed match paring (G:U wobble base pairs allowed), pattern-based sequence search based on miRNA set, free energy of miRNA-target duplex | 2011 | table of miRNA interactions with distinct target sites including miRNA-target site alignment | all target site predictions |
miRWalk [53] | stringent seed: seed match pairing within 3' UTR, 5' UTR, CDS, and promoter region | 2011 | table of miRNA-target interactions | predictions for individual miRNAs or targets |
miRmap [54] | stringent seed : seed match paring, number of target sites, target site evolutionary conservations, target site context and accessibility, ensemble free energy of miRNA-target interaction | 2013 | table of miRNA-target interactions, miRNA-target site alignment including scores for every interaction criterion | all target site predictions, algorithms (Python) |
2.2. Databases that Collect Validated Direct miRNA–mRNA Interactions
2.3. High-Throughput Experimental Methods to Identify Potential Direct Target mRNAs
2.4. Experimental Methods to Identify Individual Potential Direct Target mRNAs
3. Validation of Direct miRNA–mRNA Interactions
3.1. Reporter Gene Assays
3.2. Electrophoretic Mobility Shift Assay (EMSA)
4. Deciphering the Biological Impact of Individual miRNA–mRNA Interactions
4.1. Phenocopy Experiments
4.2. Disruption of Particular miRNA–mRNA Interactions
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Karbiener, M.; Glantschnig, C.; Scheideler, M. Hunting the Needle in the Haystack: A Guide to Obtain Biologically Meaningful MicroRNA Targets. Int. J. Mol. Sci. 2014, 15, 20266-20289. https://doi.org/10.3390/ijms151120266
Karbiener M, Glantschnig C, Scheideler M. Hunting the Needle in the Haystack: A Guide to Obtain Biologically Meaningful MicroRNA Targets. International Journal of Molecular Sciences. 2014; 15(11):20266-20289. https://doi.org/10.3390/ijms151120266
Chicago/Turabian StyleKarbiener, Michael, Christina Glantschnig, and Marcel Scheideler. 2014. "Hunting the Needle in the Haystack: A Guide to Obtain Biologically Meaningful MicroRNA Targets" International Journal of Molecular Sciences 15, no. 11: 20266-20289. https://doi.org/10.3390/ijms151120266