Abstract
MicroRNAs (miRNAs) are a class of small, well-conserved noncoding RNAs that regulate gene expression post-transcriptionally. They have been demonstrated to regulate a lot of biological pathways and cellular functions. Many miRNAs are dynamically regulated during central nervous system (CNS) development and are spatially expressed in adult brain indicating their essential roles in neural development and function. In addition, accumulating evidence strongly suggests that dysfunction of miRNAs contributes to neurological diseases. These observations, together with their gene regulation property, implicated miRNAs to be the key regulators in the complex genetic network of the CNS. In this review, we first focus on the ways through which miRNAs exert the regulatory function and how miRNAs are regulated in the CNS. We then summarize recent findings that highlight the versatile roles of miRNAs in normal CNS physiology and their association with several types of neurological diseases. Subsequently we discuss the limitations of miRNAs research based on current studies as well as the potential therapeutic applications and challenges of miRNAs in neurological disorders. We endeavor to provide an updated description of the regulatory roles of miRNAs in normal CNS functions and pathogenesis of neurological diseases.
Highlights
In a short highlight [73], the authors suggested that mitochondria are prime candidates for regulating miRNA activity based on two pieces of evidence, namely, thermodynamics of miRNA:mRNA interaction and the interaction between mitochondria and other cellular compartments, organelles and cytoplasmic foci is important for energy distribution, signaling and homeostasis
Considering the important roles of neuronal mRNA transportation, local protein synthesis and mitochondria in many events of the central nervous system (CNS) [74,75], it is worthy pointing out this highly novel dimension of gene regulation by the interaction and crosstalk between miRNA and mitochondria, and further studying how these interactions mediate responses to cellular cues in the CNS. This undiscovered mechanism in gene regulation might advance our knowledge in miRNA regulation in the CNS and bring effective means to control abnormal events happened in the CNS in future
These findings suggest the profound effect of miRNA on CNS inflammation and related neurological diseases
Summary
The pri-miRNA is cleaved in the nucleus by the endoribonuclease Drosha, a member of the RNase III proteins, into ~70 nucleotide stem-loop precursor miRNA (pre-miRNA) [4]. The product, pre-miRNA, is exported to the cytoplasm with the aids of an exportin5-Ran-GTP complex and further processed by another member of RNase III protein—Dicer into ~22 base pair miRNA/miRNA* (guided strand/passenger strand of the same hairpin structure) duplex [5,6]. The steady expression level of miRNAs is regulated by both biogenesis and degradation, the latter has received limited attention so far, partially due to the long decay period of which can be ten times longer than that of mRNAs [11]. The quick decaying response of miRNAs to physiological stimuli, including illumination change and synaptic stimulation, implicates that active miRNAs metabolism might strongly support the neuronal functions and plasticity [14]
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