It used microarrays and bioinformatics to come to an unexpected conclusion: canonical microRNA:mRNA interactions are leading to transcript degradation in animals.

miRNAs modulate many biological phenomena, including development and cancer. This paper revealed that this modulation could be detected using a commonly used technique called microarray profiling.

When we transfected muscle-specific or brain-specific miRNAs into cells and profiled their effects using microarrays, we found that information about the tissue-specificity and sequences of the miRNAs was encoded in the properties of genes whose transcripts decreased. These genes were present at lower levels in muscle or brain relative to other tissues in the human body, and the 3’ UTRs of the genes contained matches to the seed regions of the miRNA.

This led to several inferences: that miRNAs can cause transcript degradation in vivo, that they can downregulate many genes, and that, as a consequence of this prolific activity, one of their roles could be to repress a large number of genes that shouldn’t be highly expressed in that tissue.

It also suggested that microarrays could be used as a convenient tool to help investigate microRNA targeting, an application for microarrays that had been previously ignored because it had been assumed that miRNA effects were exclusively translational.

Peter Linsley’s group at Rosetta Inpharmatics LLC, had previously made the observation that microarrays could detect off-target siRNA activities that were due to the binding of siRNA to transcripts. We were very interested in miRNA targeting at the time, so it made sense to see if miRNA activity could also be detected in this manner.