Conserved expression patterns predict microRNA targets

microRNAs (miRNAs) are major regulators of gene expression and thereby modulate many biological processes. Computational methods have been instrumental in understanding how miRNAs bind to mRNAs to induce their repression but have proven inaccurate. Here we describe a novel method that combines expre...

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Bibliographic Details
Published in:PLoS computational biology 2009-09, Vol.5 (9), p.e1000513-e1000513
Main Authors: Ritchie, William, Rajasekhar, Megha, Flamant, Stephane, Rasko, John E J
Format: Article
Language:English
Subjects:
Algorithms
Animals
Computational Biology - methods
Computational Biology/Genomics
Experiments
Gene expression
Gene Expression Profiling - methods
Gene Expression Regulation
Genes, Reporter - genetics
Genetics and Genomics/Bioinformatics
Genetics and Genomics/Gene Expression
HeLa Cells
Humans
Luciferase
Luciferases - genetics
Luciferases - metabolism
Messenger RNA
Mice
MicroRNAs - genetics
Molecular Biology/Bioinformatics
Molecular Biology/mRNA Stability
Molecular Biology/Post-Translational Regulation of Gene Expression
Oligonucleotide Array Sequence Analysis - methods
Regulation
Reproducibility of Results
RNA, Messenger - genetics
ROC Curve
Statistics as Topic
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Summary:microRNAs (miRNAs) are major regulators of gene expression and thereby modulate many biological processes. Computational methods have been instrumental in understanding how miRNAs bind to mRNAs to induce their repression but have proven inaccurate. Here we describe a novel method that combines expression data from human and mouse to discover conserved patterns of expression between orthologous miRNAs and mRNA genes. This method allowed us to predict thousands of putative miRNA targets. Using the luciferase reporter assay, we confirmed 4 out of 6 of our predictions. In addition, this method predicted many miRNAs that act as expression enhancers. We show that many miRNA enhancer effects are mediated through the repression of negative transcriptional regulators and that this effect could be as common as the widely reported repression activity of miRNAs. Our findings suggest that the indirect enhancement of gene expression by miRNAs could be an important component of miRNA regulation that has been widely neglected to date.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1000513