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Comparative Study
. 2007 Jun 7:8:152.
doi: 10.1186/1471-2164-8-152.

Spatial preferences of microRNA targets in 3' untranslated regions

Affiliations
Comparative Study

Spatial preferences of microRNA targets in 3' untranslated regions

William H Majoros et al. BMC Genomics. .

Abstract

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.

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Figures

Figure 1
Figure 1
Variants of 3' untranslated regions (UTRs). Shown from the top are constitutive UTRs; type-1 alternative UTRs with multiple PAS in the same exon, and type-2 alternative UTRs with multiple PAS in different exons.
Figure 2
Figure 2
Classification of miRNA target genes. The total set of genes is grouped in different subclasses, defined by the presence of alternative UTRs and the location of target sites. Constitutive targets encompass predicted target genes with constitutive UTRs, as well as genes with alternative UTRs, in which all sites are located within the constitutive UTR regions. Alternatively targeted genes have at least one target site located in an alternative 3'UTR segment. On/off targets are alternative targets in which all target sites fall exclusively into alternative UTR regions; modulated targets contain alternative targets with sites in both constitutive and alternative UTR regions. Shown are the total number of genes in each class, as well as the relative size of the subclasses.
Figure 3
Figure 3
Examples of target classes. Screenshots from the UCSC genome browser illustrate the difference between (A) constitutive targets, (B) on/off targets and (C) alternative targets.
Figure 4
Figure 4
Length distributions of maximal 3'UTRs. (A) All genes versus miRNA targeted genes. (B) Constitutively targeted genes versus alternatively targeted genes.
Figure 5
Figure 5
Distribution of target site locations along 3'UTRs. (A) Constitutive segments. In the top panel, site locations are normalized by the UTR length and given as relative position between 0 and 1. In the bottom panel, absolute site locations within the first and last 500 nt of the UTR segments are shown. Hits are binned in 10 nt intervals. (B) Alternative segments. Top and bottom panels are as described for (A).

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