MicroRNAs in neural development: from master regulators to fine-tuners

Abstract

The proper formation and function of neuronal networks is required for cognition and behavior. Indeed, pathophysiological states that disrupt neuronal networks can lead to neurodevelopmental disorders such as autism, schizophrenia or intellectual disability. It is wellestablished that transcriptional programs play major roles in neural circuit development. However, in recent years, post-transcriptional control of gene expression has emerged as an additional, and probably equally important, regulatory layer. In particular, it has been shown that microRNAs (miRNAs), an abundant class of small regulatory RNAs, can regulate neuronal circuit development, maturation and function by controlling, for example, local mRNA translation. It is also becoming clear that miRNAs are frequently dysregulated in neurodevelopmental disorders, suggesting a role for miRNAs in the etiology and/or maintenance of neurological disease states. Here, we provide an overview of the most prominent regulatory miRNAs that control neural development, highlighting how they act as 'master regulators' or 'fine-tuners' of gene expression, depending on context, to influence processes such as cell fate determination, cell migration, neuronal polarization and synapse formation.

MiR‐181a inhibits vascular inflammation induced by ox‐LDL via targeting TLR4 in human macrophages

“…Increasing miRNAs are considered to be clinical biomarkers for atherosclerosis (Feinberg & Moore, ). Many recent studies have indicated that miRNAs can control a lot of fundamental biological processes (Rajman & Schratt, ; Zhang et al, ). For example, miR‐100 can inhibit chronic vascular inflammation by stimulating endothelial autophagy (Pankratz et al, ).…”

Dysregulation of miRNA and its potential therapeutic application in schizophrenia

“…Since then, there are numerous reports that revealed the roles of various miRNA in neuronal development and differentiation. The important functional roles of miRNA in neurogenesis, neuroprotection, survival, and pathogenesis of neuropsycho‐disorders have been also extensively studied and reviewed . In addition, alterations of miRNA are reported to be associated with many neuropsychiatric diseases.…”

“…In support, Konopka et al found the enhanced learning and memory in adult mice with tamoxifen‐induced deletion of Dicer1 gene. However, when using knockout mouse models, some consideration should be taken into account as pointed out by Rajman . Indeed, Dicer1 has been proved to be essential for cell survival and embryonic development.…”

“…From the view of pathophysiology, abnormal neurotransmission, particularly disturbed dopamine‐glutamate transmission and altered prefrontal dysfunction may play an important role in the majority of the symptoms of schizophrenia . Recent emerging evidences suggest that small noncoding RNAs known as microRNAs (miRNAs) are involved in pathogenesis and pathological process of the illness . miRNAs are a class of ~22 nucleotides noncoding RNAs, which can functionally silence gene in a post‐transcriptional manner by complementary base‐pairing with target mRNA.…”

Oxidized low‐density lipoprotein promotes vascular endothelial cell dysfunction by stimulating miR‐496 expression and inhibiting the Hippo pathway effector YAP

“…Sustained high concentrations of ox-LDL can stimulate vascular endothelial cells, upregulate the expression of the autophagy-related proteins beclin 1 and lipidated microtubule-associated protein light chain 3, increase intracellular Ca 2þ concentration, induce endoplasmic reticulum stress (ERS), and induce the expression of the pro-apoptosis proteins JNK (mitogen-activated protein kinase 8) and CHOP (DNA damage inducible transcript 3), leading to vascular endothelial cell apoptosis (Muller et al, 2011). Accumulating studies have demonstrated that miRNAs are involved in various physiological and biochemical reactions in mammals, such as stem cell pluripotency maintenance and directional differentiation regulation, organogenesis, developmental regulation, tumorigenesis and tumor progression, and the pathogenesis of ageing (Cheng et al, 2012;Liu et al, 2013;Moran et al, 2017;Rajman and Schratt, 2017). Therefore, ox-LDL plays an important role in atherosclerosis progression.…”