MikroRNA neuraalisessa kantasolussa

http://journal.frontiersin.org/Journal/10.3389/fnins.2012.00030/full

Front. Neurosci., 12 March 2012 | doi: 10.3389/fnins.2012.00030

MicroRNAs in neural stem cells and neurogenesis

Hironori Kawahara^1,2, Takao Imai¹ and Hideyuki Okano¹*

• ¹ Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan
• ² Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

MicroRNA (miRNA) is a type of short-length (~22 nt) non-coding RNA. Most miRNAs are transcribed by RNA polymerase II and processed by Drosha-DGCR8 and Dicer complexes in the cropping and dicing steps, respectively. miRNAs are exported by exportin-5 from the nucleus to the cytoplasm after cropping. Trimmed mature miRNA is loaded and targets mRNA at the 3′ or 5′ untranslated region (UTR) by recognition of base-pairing in the miRNA-loaded RISC, where it is involved in gene silencing including translational repression and/or degradation along with deadenylation. Recent studies have shown that miRNA participates in various biological functions including cell fate decision, developmental timing regulation, apoptosis, and tumorigenesis. Analyses of miRNA expression profiles have demonstrated tissue- and stage-specific miRNAs including the let-7 family, miR-124, and miR-9, which regulate the differentiation of embryonic stem cells and/or neurogenesis. This review focuses on RNA-binding protein-mediated miRNA biogenesis during neurogenesis. These miRNA biogenesis-relating proteins have also been linked to human diseases because their mutations can cause several nervous system disorders. Moreover, defects in core proteins involved in miRNA biogenesis including Drosha, DGCR8, and Dicer promote tumorigenesis. Thus, the study of not only mature miRNA function but also miRNA biogenesis steps is likely to be important.

Figure 4. The regulatory loop between miRNAs and their regulators in NSC differentiation and neuronal maturation. (A) Negative feedback regulatory loop of miR-9 and TLX. TLX recruits HDAC5 to the miR-9 locus to inhibit miR-9 expression. MiR-9 can repress the level of TLX through its 3′ UTR. At the same time, LSD1 may be recruited. (B) TLX recruits LSD1 to the miR-137 locus to inhibit miR-137 expression. The expression of miR-137 can repress the level of LSD1. Similarly, HDAC5 may be recruited. (C) Transcription factor Pitx3 promotes miR-133b expression, while miR-133b can down-regulate Pitx3 level.