miRNA sponges: soaking up miRNAs for regulation of gene expression

MicroRNAs (miRNAs) are small regulatory RNAs that act in an entangled web of interactions with target mRNAs to shape the cellular protein landscape by post‐transcriptional control of mRNA decay and translation. miRNAs are themselves subject to numerous regulatory mechanisms that adjust their prevalence and activity. Emerging evidence suggests that miRNAs are themselves targeted by regulatory RNA species, and the identification of several classes of noncoding RNA molecules carrying miRNA binding sites has added a new intricate dimension to miRNA regulation. Such miRNA ‘sponges’ bind miRNAs and competitively sequester them from their natural targets. Endogenous miRNA sponges, also termed competing endogenous RNAs (ceRNAs), act to buffer the activity of miRNAs on physiologically relevant targets. This class of sponges includes endogenously transcribed pseudogenes, long noncoding RNAs, and recently discovered circular RNAs and may act in large complex networks in conjunction with miRNAs to regulate the output of protein. With the growing demand of regulating miRNA activity for experimental purposes and potential future clinical use, naturally occurring miRNA sponges are providing inspiration for engineering of gene vector‐encoded sponges as potent inhibitors of miRNA activity. Combined with potent and versatile vector technologies, expression of custom‐designed sponges provides new means of managing miRNAs and soaking up miRNAs for therapeutic regulation of gene expression.