Using miR-125b and let-7 as representative miRNAs, Wu et al45 showed that in mammalian cells the reduction in mRNA abundance is a consequence of accelerated deadenylation, which leads to rapid mRNA decay. Besides regulating translational processes, it has been shown that miRNA can also regulate gene transcription by targeting transcription factors. In this case, levels of transcription factors are downregulated by miRNAs, which in turn cause less expression of mRNA, leading to reduced Inhibitors,research,lifescience,medical protein synthesis.46,47 Recent evidence suggests that miRNA biogenesis can be regulated at the epigenetic level.48 For example, inhibitors of

DNA methylation and lifescience histone deacetylases can affect expression of several miRNAs.49 On the other hand, Inhibitors,research,lifescience,medical a subset of miRNAs can control the expression of epigenetic regulators, such as DNA methyltransferases, histone deacetylases, and polycomb group genes, leading to transcriptional activation of numerous protein coding gene sequences, thereby contributing to gene expression. This network of feedback

between miRNAs and epigenetic pathways appears to form an epigenetics-miRNA regulatory circuit, and to organize the whole gene expression profile.50 The expression of miRNAs is tissue-specific51-53 and, in some cases, even cell-type-specific.54-56 In addition, some of the miRNAs are expressed specifically Inhibitors,research,lifescience,medical at the developmental stages.57,58 Approximately 20% to 40% of miRNAs in the brain are developmentally regulated.59,60 For example, miR-124a, which is conserved at the nucleotide level and is important for neuronal differentiation, neurite outgrowth, Inhibitors,research,lifescience,medical and glucocorticoid receptor (GR)—mediated functions, is expressed throughout embryonic and adult brain.61,62 There are studies which suggest that miRNAs, such as miR-124 and miR-128, are primarily expressed in neurons, whereas miR-23, miR-26, and miR-29 are expressed in high amounts in astrocytes.63 A recent study by He et al64 Inhibitors,research,lifescience,medical suggests that

a large number of miRNAs show distinct profiles in glutamatergic and GABAergic neurons and subtypes ALOX15 of GABAergic neurons. Even within neurons, it has been demonstrated that some of the pre-miRNAs are highlyexpressed in the dendrites where they can be locally transcribed into mature miRNAs65 and can locally regulate mRNA translation. These include synaptically enriched miRNAs: miR-200c, miR-339, miR-332, miR-318, miR-29a, miR-7, and miR-137.65,66 Several of the miRNAs are also expressed in the exons and presynaptic nerve terminals; some of them (miR-16, miR-221, miR-204, miR-15b) are highly expressed in distal axons compared with cell bodies.67 Moreover, a number of miRNAs encoded by a common pri-miRNA were differentially expressed in the distal axons, suggesting that there is a differential subcellular transport of miRNAs derived from the same coding region of the genome.