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

MicroRNAs are noncoding RNAs, approximately 22nt in length, which serve to negatively regulate gene expression through binding to complementary sequences in the 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, therefore 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, therefore 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. Abstract figure legend MicroRNAs are short noncoding RNAs which negatively regulate gene expression via targeting of complementary sequences, primarily in the 3' untranslated region, of mRNA transcripts. There are hundreds of different microRNAs and each has a target pool which can comprise many different gene transcripts. Many microRNA-target interactions have been identified which can modulate neural excitability, with impacts on processes including synaptic transmission and plasticity, ion transporters, and voltage-gated ion channels. The expression of many microRNAs is in turn regulated by neuronal activity and therefore forms feedback loops. This article is protected by copyright. All rights reserved.