Spatial preferences of microRNA targets in 3′ untranslated regions

Background: MicroRNAs are an important class of regulatory RNAs which repress animal genes by preferentially interacting with complementary sequence motifs in the 3 ' untranslated region (UTR) of target mRNAs. Computational methods have been developed which can successfully predict which microRNA may target which mRNA on a genome-wide scale. Results: We address how predicted target sites may be affected by alternative polyadenylation events changing the 3 ' UTR sequence. We find that two thirds of targeted genes have alternative 3 ' UTRs, with 40% of predicted target sites located in alternative UTR segments. We propose three classes based on whether the target sites fall within constitutive and/or alternative UTR segments, and examine the spatial distribution of predicted targets in alternative UTRs. In particular, there is a strong preference for targets to be located in close vicinity of the stop codon and the polyadenylation sites. Conclusion: The transcript diversity seen in non-coding regions, as well as the relative location of miRNA target sites defined by it, has a potentially large impact on gene regulation by miRNAs and should be taken into account when defining, predicting or validating miRNA targets.