Alternative polyadenylation sites produce transcript isoforms with 3 untranslated regions (UTRs) of different lengths. If
a microRNA (miRNA) target is present in the UTR, then only those target-
containing isoforms should be sensitive to control by a cognate miRNA. We carried out a systematic examination of 3 UTRs containing multiple poly(A) sites and putative miRNA targets. Based on expressed sequence tag (EST) counts and EST library information, we observed that levels of isoforms containing targets for miR-1 or miR-124, two miRNAs causing downregulation of transcript levels, were reduced in tissues expressing the corresponding miRNA. This analysis was repeated for all
conserved 7-mers in 3 UTRs, resulting in a selection of 312 motifs. We show that this set is significantly enriched in known miRNA targets and mRNA-destabilizing elements, which validates our initial hypothesis. We scanned the human genome for possible cognate miRNAs and identified phylogenetically conserved precursors matching our motifs. This analysis can help identify target-miRNA couples that went undetected in previous screens, but it may also reveal targets for other types of regulatory factors.