Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting
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Summary

MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development鈥攚ith its resulting diversity of cellular contexts鈥攊mpacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3鈥?UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3鈥?UTR isoforms revealed that they influence 鈭?0% of predicted targets when comparing any two cell types. Indeed, considering alternative 3鈥?UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3鈥?UTR landscape helps predict targeting efficacy and explain differential regulation that is observed.

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