Properties of the regulatory RNA-binding protein HuR and its role in controlling miRNA repression.

Gene expression in eukaryotes is subject to extensive regulation at posttranscriptional levels. One of the most important sites of control involves mRNA 3' untranslated regions (3'UTRs), which are recognized by RNA-binding proteins (RBPs) and microRNAs (miRNAs). These factors greatly influence translational efficiency and stability of target mRNAs and often also determine their cellular localization. HuR, a ubiquitously expressed member of the ELAV family of RBPs, has been implicated in regulation of stability and translation of over one hundred mRNAs in mammalian cells. Recent data indicate that some of the effects of HuR can be explained by its interplay with miRNAs. Binding of HuR may suppress the inhibitory effect of miRNAs interacting with the 3'UTR and redirect the repressed mRNA to polysomes for active translation. However, HuR can also synergize with miRNAs. The finding that HuR is able to disengage miRNAs from the repressed mRNA, or render them inactive, provides evidence that miRNA regulation is much more dynamic then originally anticipated. In this chapter we review properties of HuR and describe examples of the cross-talk between the protein and miRNAs, with emphasis on response of the regulation to cellular stress.