A role for miR-19 in the migration of adult-born neurons and schizophrenia.

Neurogenesis (Austin, Tex.) Pub Date : 2016-12-05 eCollection Date: 2016-01-01 DOI:10.1080/23262133.2016.1251873
Jinju Han, Fred H Gage
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引用次数: 12

Abstract

The latest miRNA database (Release 21) annotated 2588 and 1915 miRNAs in the human and mouse genomes, respectively.1 However, the biological roles of miRNAs in vivo remain largely unknown. In particular, the physiological and pathological roles of individual microRNAs in the brain have not been investigated extensively although expression profiles of microRNAs have been reported in many given conditions. In a recent study,2 we identified miR-19, which is enriched in adult hippocampal neural progenitor cells (NPCs), as a key regulator for adult hippocampal neurogenesis. miR-19 is an intrinsic factor regulating the migration of newborn neurons by modulating expression level of RAPGEF2. After observing the abnormal expression patterns of miR-19 and RAPGEF2 in NPCs derived from induced pluripotent stem cells of schizophrenic patients, which display aberrant cell migration, we proposed miR-19 as a molecule associated with schizophrenia. The results illustrate that a single microRNA has the potential to impact the functions of the brain. Identifying miRNA-mediated posttranscriptional gene regulation in the brain will expand our understanding of brain development and functions and the etiologies of several brain disorders.

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miR-19在成人神经元迁移和精神分裂症中的作用。
最新的miRNA数据库(Release 21)分别在人类和小鼠基因组中标注了2588个和1915个miRNA然而,mirna在体内的生物学作用在很大程度上仍然未知。特别是,尽管在许多特定条件下已经报道了microrna的表达谱,但个体microrna在大脑中的生理和病理作用尚未得到广泛研究。在最近的一项研究中,我们发现miR-19在成人海马神经祖细胞(npc)中富集,是成人海马神经发生的关键调节因子。miR-19是通过调节RAPGEF2表达水平调控新生神经元迁移的内在因子。在观察到miR-19和RAPGEF2在精神分裂症患者诱导多能干细胞衍生的npc中的异常表达模式,并表现出异常的细胞迁移后,我们提出miR-19可能是精神分裂症的相关分子。结果表明,单个microRNA具有影响大脑功能的潜力。鉴定大脑中mirna介导的转录后基因调控将扩大我们对大脑发育和功能以及几种脑部疾病病因的理解。
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