Essential function, sophisticated regulation and pathological impact of the selective RNA-binding protein QKI in CNS myelin development.
Essential function, sophisticated regulation and pathological impact of the selective RNA-binding protein QKI in CNS myelin development.
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DOI：
10.2217/14796708.3.6.655
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发表时间：
2008-11
期刊：
影响因子：
1.3
通讯作者：
Feng Y
中科院分区：
文献类型：
--
作者：
Bockbrader K;Feng Y
选择性RNA结合蛋白QKI在促进少突胶质细胞依赖的髓鞘形成中起关键作用，而少突胶质细胞依赖的髓鞘形成对中枢神经系统的功能和发育至关重要。新的证据表明，QKI异常与精神分裂症有关，并可能导致这种毁灭性疾病的髓鞘损伤，这极大地增加了人们对QKI功能的了解兴趣。尽管已经发现了QKI-RNA相互作用的生化基础，但目前还没有一个全面的模型来说明QKI如何调节其mRNA配体以促进正常的髓鞘生成，以及QKI途径的缺陷如何参与影响中枢神经系统髓鞘的人类疾病的发病机制。在这篇综述中，我们将集中于QKI在促进少突胶质细胞分化和髓鞘形成的关键发育阶段调节不同的mRNA靶标中的作用。此外，我们还将讨论在正常髓鞘形成过程中控制QKI表达和活性的分子机制，以及QKI缺陷对髓鞘功能障碍突变动物和人类髓鞘疾病的病理影响。
The selective RNA-binding protein QKI play a key role in advancing oligodendrocyte-dependent myelination, which is essential for the function and development of the CNS. The emerging evidence that QKI abnormalities are associated with schizophrenia and may underlie myelin impairment in this devastating disease has greatly increased interest in understanding the function of QKI. Despite the discovery of the biochemical basis for QKI-RNA interaction, a comprehensive model is currently missing regarding how QKI regulates its mRNA ligands to promote normal myelinogenesis and how deficiency of the QKI pathway is involved in the pathogenesis of human diseases that affect CNS myelin. In this review, we will focus on the role of QKI in regulating distinct mRNA targets at critical developmental steps to promote oligodendrocyte differentiation and myelin formation. In addition, we will discuss molecular mechanisms that control QKI expression and activity during normal myelinogenesis as well as the pathological impact of QKI deficiency in dysmyelination mutant animals and in human myelin disorders.