Competition and collaboration between RNA-binding proteins and microRNAs

Posttranscriptional regulation of mRNA species represents a major regulatory checkpoint in the control of gene expression. Historically, RNA-binding proteins (RBPs) have been regarded as the primary regulators of mRNA stability and translation. More recently, however, microRNAs have emerged as a class of potent and pervasive posttranscriptional rheostats that similarly affect mRNA stability and translation. The observation that both microRNAs and RBPs regulate mRNA stability and translation has initiated a newer area of research that involves the examination of dynamic interactions between these two important classes of posttranscriptional regulators, the myriad of factors that influence these biological interactions, and ultimately, their effects on target mRNAs. Specifically, microRNAs and RBPs can act synergistically to effect mRNA destabilization and translational inhibition. They can also engage in competition with each other and exert opposing effects on target mRNAs. To date, several key studies have provided critical details regarding the mechanisms and principles of interaction between these molecules. Additionally, these findings raise important questions regarding the regulation of these interactions, including the roles of posttranslational modification, subcellular localization, target inhibition versus activation, and changes in expression levels of these regulatory factors, especially under stimulus- and cell-specific conditions. Indeed, further experimentation is warranted to address these key issues that pertain to the collaboration and competition between microRNAs and RBPs. Significantly, the elucidation of these important details bears critical implications for disease management, especially for those diseases in which these cellular factors are dysregulated. (C) 2013 John Wiley & Sons, Ltd.