MicroRNAs: Meta-controllers of gene expression in synaptic activity emerge as genetic and diagnostic markers of human disease.

MicroRNAs are members of the non-protein-coding family of RNAs. They serve as regulators of gene expression by modulating the translation and/or stability of messenger RNA targets. The discovery of microRNAs has revolutionized the field of cell biology, and has permanently altered the prevailing view of a linear relationship between gene and protein expression. The increased complexity of gene regulation is both exciting and daunting, as emerging evidence supports a pervasive role for microRNAs in virtually every cellular process. This review briefly describes microRNA processing and formation of RNA-induced silencing complexes, with a focus on the role of RNA binding proteins in this process. We also discuss mechanisms for microRNA-mediated regulation of translation, particularly in dendritic spine formation and function, and the role of microRNAs in synaptic plasticity. We then discuss the evidence for altered microRNA function in cognitive brain disorders, and the effect of gene mutations revealed by single nucleotide polymorphism analysis on altered microRNA function and human disease. Further, we present evidence that altered microRNA expression in circulating fluids such as plasma/serum can correlate with, and serve as, novel diagnostic biomarkers of human disease.