MicroRNAs - small RNAs with a big influence on brain excitability.

Abstract

MicroRNAs are non-coding RNAs, approximately 22nt in length, which serve to negatively regulate gene expression through binding to complementary sequences in the 3' untranslated region (3'UTR) of target mRNA. The microRNA-target interaction does not require perfect complementarity, meaning that an individual microRNA often has a pool of hundreds of gene targets. Equally, one 3'UTR can contain target sites for many different microRNAs. This gives rise to a complex web of molecular interactions. An emerging concept is that microRNAs have a role as 'master' regulators of certain cellular properties, simultaneously mediating the subtle repression of multiple related genes within a pathway or system, thereby achieving a common phenotypic output. One such example is regulation of brain excitability. There are numerous examples of microRNAs which can target ion channels, ion transporters and genes associated with synaptic transmission. Often, the expression of the microRNA itself is regulated in an activity-dependent manner, thereby forming homeostatic loops. Limitations in our understanding arise from the sheer complexity of microRNA-target interactions, which are difficult to capture experimentally and computationally. Further, many microRNA studies rely on animal model systems, but many microRNAs (and mRNA targets) have sequences which are either not conserved or are entirely unique in the human brain. This leaves many exciting and challenging opportunities to further progress the field in an attempt to fully understand the roles of microRNAs in brain function.