A structural-based statistical approach suggests a cooperative activity of PUM1 and miR-410 in human 3'-untranslated regions

We analyzed human 3'-UTR sequences containing potential binding sites of 153 conserved miRNA families, and ranked sequences around the sites according to their miRNA accessibility. By applying a rank-based motif search tool to these miRNA targets, we found motifs that are enriched among less accessible targets. As expected from our ranking method, most of the significant motifs were GC-rich. However, one AU-rich motif was found to be enriched among miR-410 less accessible targets. This motif resembles the Pumilio homolog 1 (PUM1) consensus binding site. We observed a stronger enrichment of the PUM1 motif in conserved targets than in non-conserved targets; moreover, the enrichment of this motif was found to be conserved in a subset of placental mammals. Further, we analyzed publicly available gene expression data, and found that the mutual expression of PUM1 and miR-410 has a greater negative influence on the expression of low accessibility targets than on other targets, an effect that was stronger than when considering both miR-410 and PUM1 separately.Taken together, our findings suggest a cooperative relationship between miR-410 and PUM1 in regulating human highly structured 3'-UTRs. This kind of cooperation can allow a second level of regulation of such targets. Considering cases in which miRNAs bind low accessibility targets may help to improve current miRNA prediction tools and to obtain a better understanding of the mechanisms underlying miRNA regulation activity.Micro (mi)RNAs are small RNA molecules (approximately 22 nucleotides) participating in a large variety of cellular processes in animals, plants and viruses [1-3]. miRNAs act by binding to the 3'-untranslated region (3'-UTR) of messenger (m)RNAs, forming hybrids that consist of the binding site in the 3'-UTR and of the miRNA seed region (positions 2-8 in the miRNA) [4,5]. miRNAs regulate mRNAs through two main mechanisms: mRNA degradation and inhibition of mRNA translation [6]. It has been shown that th