MicroRNAs in Neural Stem Cells and Neurogenesis.

MicroRNAs in Neural Stem Cells and Neurogenesis.
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DOI:
10.3389/fnins.2012.00030
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发表时间:
2012
影响因子:
4.3
通讯作者:
Okano H
Okano H
中科院分区:
医学2区
文献类型:
--
作者:
Kawahara H;Imai T;Okano H

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MicroRNA(miRNA)是一类长度较短(约22 nt)的非编码RNA。大多数miRNA由RNA聚合酶II转录,并分别在剪切和切割步骤中由Drosha-DGCR 8和Dicer复合物加工。在剪切后,miRNA通过输出蛋白-5从细胞核输出到细胞质。通过识别加载miRNA的RISC中的碱基配对,加载并靶向3′或5′非翻译区(UTR)的mRNA,其中它参与基因沉默,包括翻译抑制和/或降解沿着去腺苷化。最近的研究表明,miRNA参与了多种生物学功能,包括细胞命运决定、发育时序调节、凋亡和肿瘤发生。对miRNA表达谱的分析已经证明了组织和阶段特异性miRNA,包括let-7家族、miR-124和miR-9,其调节胚胎干细胞的分化和/或神经发生。本文就神经发生过程中RNA结合蛋白介导的miRNA生物合成进行综述。这些与miRNA生物发生相关的蛋白质也与人类疾病有关,因为它们的突变可能导致几种神经系统疾病。此外,参与miRNA生物发生的核心蛋白(包括Drosha、DGCR 8和Dicer)的缺陷促进肿瘤发生。因此,不仅研究成熟的miRNA功能,而且研究miRNA的生物发生步骤可能是重要的。
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.
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