Differential repression of alternative transcripts: A screen for miRNA targets

Alternative polyadenylation sites produce transcript isoforms with 39 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 39 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 39 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.