In the past decade, it has become evident that beyond the primary mechanisms of gene regulation, a secondary layer of regulation exists, which is mediated by microRNAs (miRNAs). Previously too small to detect, and later believed to be transcriptional junk, thousands of different miRNAs have now been identified in human cells as major determinants of protein output and cell homeostasis.
As if this regulatory network was not intricate enough, a third layer of regulation has recently been identified in which the miRNAs themselves are subject to regulation. miRNAs act by guiding protein complexes to protein-coding mRNA transcripts mainly by means of imperfect RNA-RNA base pairing. In our recent review in WIREs RNA, we describe different classes of Sponge RNAs, both artificial and endogenous RNAs that carry miRNA binding sites and have the ability to bind and modulate the regulatory activity of miRNAs. Such Sponge RNAs sequester the miRNAs and dilute their effective numbers. Occurring naturally in cells, ‘sponging’ can be exhibited by protein-encoding RNA transcripts, the levels of which can vary so drastically that it impacts miRNA availability and thus the regulation of other less abundant miRNA targets. Also, pseudogenes and long non-coding RNA transcripts have been identified as Sponges or ‘competing endogenous RNAs’ (ceRNAs) as they have also been termed. The abundance and significance of endogenous Sponges are only now being unraveled, but it is evident that these transcripts have the capacity to impact miRNA activity, which in turn can modulate cellular functions and ultimately contribute to diseases. /Jacob Giehm Mikkelsen
Rasmus O. Bak and Jacob Giehm Mikkelsen. miRNA sponges: soaking up miRNAs for regulation of gene expression. WIREs RNA 2014.