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. 2005 Oct 25;102(43):15557-62.
doi: 10.1073/pnas.0507443102. Epub 2005 Oct 17.

Human microRNAs target a functionally distinct population of genes with AT-rich 3' UTRs

Harlan Robins  1 , William H Press
Affiliations

Human microRNAs target a functionally distinct population of genes with AT-rich 3' UTRs

Harlan Robins et al. Proc Natl Acad Sci U S A. .

Abstract

While investigating microRNA targets, we have found that human genes divide into two roughly equal populations, based on the fraction of A plus T bases in their 3' UTRs. Using the Gene Ontology database, we find significant functional differences between the two gene populations, with AT-rich genes implicated in transcription and translation processes, and GC-rich genes implicated in signal transduction and posttranslational protein modification. Better understanding of the background distribution of nucleotides in 3' UTRs may allow improved prediction of microRNA-targeted genes in humans. We predict at least 1,200 KnownGene transcripts to be regulated by microRNAs. The large majority of these microRNA targets are in the AT-rich 3' UTR population. However, notwithstanding this preference for AT-rich targets, microRNA targets are found preferentially to be regulatory genes themselves, including both transcription factors and posttranslational modifiers. These results suggest that some processes involving mRNA, of which microRNA regulation may be just one, require AT-richness of 3' UTRs for functionality. A relationship, not simply one-to-one, between these 3' UTR populations and large-scale genomic isochores is described.

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Figures

Fig. 1.
Fig. 1.
Composition of human 3′ UTRs with A + T on the horizontal axis and C – G on the vertical axis. (Top) All human genes are plotted in red. The red ellipses are 2-σ contours of the maximum likelihood Gaussian mixture model with two components. (Middle) Invertebrates, including C. elegans and D. melanogaster, do not evidence more than a single population when plotted on the same axes. (Bottom) Same as Top (light red) with probable miRNA target genes now plotted in green (Lewis et al. “high signal-to-noise” set; ref. 6) and blue (probable targets as determined by the methods of this paper). miRNA targets lie in the right (AT-rich) component with ≈3:1 selectivity.
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