General hallmarks of microRNAs in brain evolution and development

Abstract

MicroRNAs (miRNAs) are endogenous, small non-coding RNA molecules that mediate post-transcriptional gene suppression by incomplete matches with their host mRNAs. In the central nervous system, miRNAs that functionally interact with their target genes constitute a flexible, robust and buffered regulatory network, exerting diverse roles in brain evolution and development. However, distinct variation either in hub miRNA expression levels or patterns may initiate and/or progress various adult-onset nerve-related diseases. In this review, we will summarize the current knowledge about the general hallmarks of brain miRNAs that act as vital determinants in increasingly complicated neural activities. We endeavor to provide a constructive insight into the neuroscience research in the quest to comprehend molecular underpinnings of physiological functions and pathological disorders in central nervous system.

Keywords: central nervous system; development; evolution; small non-coding RNA.

Figure 1.

Overview of the generation and functional mechanism of mature miRNA. The sequence of the entire process is ordered by the arrow.

Figure 2.

Percentage of miRNAs expressed in different areas of the brain and the related neuro-physiological functions.

Figure 3.

Principal mechanisms of miR-941 and miR-1202 in neural activities. (A) miR-941 inhibits the expression of its host gene DNAJC5. DNAJC5, coupled with its directly interacted gene RAB3A and indirectly interacted gene WDR7, is associated with neurotransmitter release. (B) miR-1202 expression is decreased in the donor brain with depression compared with the normal control. While the host gene expression of miR-1202, GRM4, is increased in the donor brain with depression. GRM4 is expressed throughout the brain and is associated with glutamatergic, dopaminergic, GABAergic and serotonergic neurotransmission.

Figure 4.

Sketch map of the spatiotemporal regulation pattern of brain miRNAs. The thickness of the arrow is positively correlated with the number of differentially expressed miRNAs during the transition from one period to another. The rightmost diagram with different color areas represents a region-specific expression pattern of brain miRNAs.