Two sets of tools that explore the function of microRNAs in human cells are reported this week in Nature Methods. The new resources will help to unravel how microRNAs, which play an important role in regulating gene expression, function on a much larger scale than was previously possible.

One of the tools offered by Brian Brown and colleagues is a library of virus vectors that can be introduced into cells to ‘sense’ the presence and activity of the vast majority of human microRNAs. Their assay, called Sensor-seq, uses the sensory library to provide a snapshot of microRNA activity in a given cell type in a single rapid experiment. The other tool is a series of ‘decoys’, each of which can bind a specific microRNA and inhibit its activity so that researchers can learn its function-a technique analogous to gene knockout.

Unlike what is generally assumed, the researchers found that the majority of microRNAs detected in cells have no effect on the expression of their target genes because they exist below a threshold required for activity. Sensor-seq also reveals which microRNAs have activity that is specific to certain tissues. Including target sites for these in engineered viruses or plasmids can selectively remove the engineered vectors from those tissues.