Transcriptome-wide prediction of miRNA targets in human and mouse using FASTH

Ragan, Chikako, Cloonan, Nicole, Grimmond, Sean M., Zuker, Michael and Ragan, Mark A. (2009) Transcriptome-wide prediction of miRNA targets in human and mouse using FASTH. PLoS One, 4 5: e5745.1-e5745.22. doi:10.1371/journal.pone.0005745

Author Ragan, Chikako
Cloonan, Nicole
Grimmond, Sean M.
Zuker, Michael
Ragan, Mark A.
Title Transcriptome-wide prediction of miRNA targets in human and mouse using FASTH
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2009-05-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0005745
Open Access Status DOI
Volume 4
Issue 5
Start page e5745.1
End page e5745.22
Total pages 22
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Abstract Transcriptional regulation by microRNAs (miRNAs) involves complementary base-pairing at target sites on mRNAs, yielding complex secondary structures. Here we introduce an efficient computational approach and software (FASTH) for genome-scale prediction of miRNA target sites based on minimizing the free energy of duplex structure. We apply our approach to identify miRNA target sites in the human and mouse transcriptomes. Our results show that short sequence motifs in the 5′ end of miRNAs frequently match mRNAs perfectly, not only at validated target sites but additionally at many other, energetically favourable sites. High-quality matching regions are abundant and occur at similar frequencies in all mRNA regions, not only the 3′UTR. About one-third of potential miRNA target sites are reassigned to different mRNA regions, or gained or lost altogether, among different transcript isoforms from the same gene. Many potential miRNA target sites predicted in human are not found in mouse, and vice-versa, but among those that do occur in orthologous human and mouse mRNAs most are situated in corresponding mRNA regions, i.e. these sites are themselves orthologous. Using a luciferase assay in HEK293 cells, we validate four of six predicted miRNA-mRNA interactions, with the mRNA level reduced by an average of 73%. We demonstrate that a thermodynamically based computational approach to prediction of miRNA binding sites on mRNAs can be scaled to analyse complete mammalian transcriptome datasets. These results confirm and extend the scope of miRNA-mediated species- and transcript-specific regulation in different cell types, tissues and developmental conditions.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # e5745

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 19 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 23 times in Scopus Article | Citations
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Created: Sun, 17 Jan 2010, 10:00:58 EST