MicroRNAs – small RNAs with a big influence on brain excitability

Abstract

MicroRNAs are non‐coding RNAs, approximately 22 nt 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.

MicroRNAs in meningiomas: Potential biomarkers and therapeutic targets

“…The World Health Organization (WHO) classification, primarily based on morphological parameters, has yet to suggest changes in the grading of meningiomas despite significant advances in understanding the molecular mechanisms of tumorigenesis and meningioma progression [ 7 ]. However, the analysis of chromosomal regions and the study of new genes are expected to contribute to future diagnosis and prognosis [ 8 ]. Molecular markers may eventually facilitate the combination of histological and molecular criteria in the classification of meningiomas [ 9 ].…”

Integrative network analysis of miRNA-mRNA expression profiles during epileptogenesis in rats reveals therapeutic targets after emergence of first spontaneous seizure

“…Due to imperfect base pairing between miRNAs and their mRNA targets, an individual miRNA can repress many different mRNAs, and individual mRNAs can be targeted by multiple miRNAs 10 – 13 . This multi-targeting property is appealing for anti-epileptogenesis therapy 14 or for treating the complex and multifaceted pathophysiology of temporal lobe epilepsy (TLE), a highly pharmacoresistant epilepsy 15 . Indeed, many of the dysregulated gene networks in TLE are known or predicted targets of miRNAs and there is also extensive dysregulation of miRNA levels in experimental and human TLE 16 – 21 .…”

MicroRNA-335-5p suppresses voltage-gated sodium channel expression and may be a target for seizure control

“…As miRNAs regulate multiple gene pathways simultaneously ( 12 ), they are an attractive target in the treatment of epilepsy where complex and diverse mechanisms give rise to imbalances between excitation and inhibition ( 13 ). This includes modulating the expression of voltage-gated ion channels ( 14 , 15 ). For example, Sosanya et al reported that miR-129 regulated the expression of Kcna1 , encoding the voltage-gated potassium channel K V 1.1 ( 16 ).…”