Individual mRNA expression profiles reveal the effects of specific microRNAs.
BACKGROUND
MicroRNAs (miRNAs) are oligoribonucleotides with an important role in regulation of gene expression at the level of translation. Despite imperfect target complementarity, they can also significantly reduce mRNA levels. The validity of miRNA target gene predictions is difficult to assess at the protein level. We sought, therefore, to determine whether a general lowering of predicted target gene mRNA expression by endogenous miRNAs was detectable within microarray gene expression profiles.


RESULTS
The target gene sets predicted for each miRNA were mapped onto known gene expression data from a range of tissues. Whether considering mean absolute target gene expression, rank sum tests or 'ranked ratios', many miRNAs with significantly reduced target gene expression corresponded to those known to be expressed in the cognate tissue. Expression levels of miRNAs with reduced target mRNA levels were higher than those of miRNAs with no detectable effect on mRNA expression. Analysis of microarray data gathered after artificial perturbation of expression of a specific miRNA confirmed the predicted increase or decrease in influence of the altered miRNA upon mRNA levels. Strongest associations were observed with targets predicted by TargetScan.


CONCLUSIONS
We have demonstrated that the effect of a miRNA on its target mRNAs' levels can be measured within a single gene expression profile. This emphasizes the extent of this mode of regulation in vivo and confirms that many of the predicted miRNA-mRNA interactions are correct. The success of this approach has revealed the vast potential for extracting information about miRNA function from gene expression profiles.
Arora
Amit
A
Queen's University Belfast, Centre for Vision Sciences, Institute of Clinical Science, Royal Victoria Hospital, Belfast BT12 6BA, UK. aarora01@qub.ac.uk
Simpson
David Ac
DA
D000465:Algorithms; D000818:Animals; D019295:Computational Biology; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics*
D035683:MicroRNAs; D012333:RNA, Messenger