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大脑中的RNA:大脑皮层发育中转录后调控的新层次

RNA on the brain: emerging layers of post-transcriptional regulation in cerebral cortex development.

作者信息

Lennox Ashley L, Mao Hanqian, Silver Debra L

机构信息

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC, USA.

Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, USA.

出版信息

Wiley Interdiscip Rev Dev Biol. 2018 Jan;7(1). doi: 10.1002/wdev.290. Epub 2017 Aug 24.

Abstract

Embryonic development is a critical period during which neurons of the brain are generated and organized. In the developing cerebral cortex, this requires complex processes of neural progenitor proliferation, neuronal differentiation, and migration. Each step relies upon highly regulated control of gene expression. In particular, RNA splicing, stability, localization, and translation have emerged as key post-transcriptional regulatory nodes of mouse corticogenesis. Trans-regulators of RNA metabolism, including microRNAs (miRs) and RNA-binding proteins (RBPs), orchestrate diverse steps of cortical development. These trans-factors function either individually or cooperatively to influence RNAs, often of similar classes, termed RNA regulons. New technological advances raise the potential for an increasingly sophisticated understanding of post-transcriptional control in the developing neocortex. Many RNA-binding factors are also implicated in neurodevelopmental diseases of the cortex. Therefore, elucidating how RBPs and miRs converge to influence mRNA expression in progenitors and neurons will give valuable insights into mechanisms of cortical development and disease. WIREs Dev Biol 2018, 7:e290. doi: 10.1002/wdev.290 This article is categorized under: Gene Expression and Transcriptional Hierarchies > Regulatory RNA Nervous System Development > Vertebrates: Regional Development Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease.

摘要

胚胎发育是一个关键时期,在此期间大脑神经元得以生成和组织。在发育中的大脑皮层,这需要神经祖细胞增殖、神经元分化和迁移等复杂过程。每一步都依赖于基因表达的高度调控。特别是,RNA剪接、稳定性、定位和翻译已成为小鼠皮质发生过程中关键的转录后调控节点。RNA代谢的反式调节因子,包括微小RNA(miRs)和RNA结合蛋白(RBPs),协调着皮质发育的不同步骤。这些反式因子单独或协同发挥作用以影响RNA,这些RNA通常属于相似类别,称为RNA调节子。新的技术进展增加了对发育中的新皮层转录后调控进行日益深入理解的可能性。许多RNA结合因子也与皮质的神经发育疾病有关。因此,阐明RBPs和miRs如何共同影响祖细胞和神经元中的mRNA表达,将为皮质发育和疾病的机制提供有价值的见解。WIREs发育生物学2018年,7:e290。doi:10.1002/wdev.290 本文分类如下:基因表达与转录层次>调控RNA;神经系统发育>脊椎动物:区域发育;成体干细胞、组织更新与再生>干细胞与疾病。

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