Splicing factor TRA2B is required for neural progenitor survival.

Splicing factor TRA2B is required for neural progenitor survival.
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DOI:
10.1002/cne.23405
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发表时间:
2014-02-01
影响因子:
2.5
通讯作者:
Chen, Bin
Chen, Bin
中科院分区:
医学3区
文献类型:
--
作者:
Roberts, Jacqueline M.;Ennajdaoui, Hanane;Edmondson, Carina;Wirth, Brunhilde;Sanford, Jeremy R.;Chen, Bin

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前体mRNA的选择性剪接可以快速调节大量蛋白质的表达。RNA结合蛋白TRA 2B(SFRS 10)在果蝇性别分化过程中的发育调控选择性剪接中发挥着重要作用。TRA 2B也是哺乳动物胚胎发生所必需的,并与许多人类疾病有关。选择性剪接的精确调控对中枢神经系统的发育和功能至关重要;然而,对神经发生中特定剪接因子的需求知之甚少。在这项研究中,我们专注于TRA 2B在哺乳动物大脑发育中的作用。我们发现,在小鼠皮层神经发生,TRA 2B表达在神经祖细胞和皮层投射神经元。使用皮质特异性Tra 2b突变小鼠,我们发现TRA 2B耗竭导致神经前体细胞凋亡以及皮质板的解体。因此,TRA 2B对大脑皮层的正常发育至关重要。
Alternative splicing of pre-mRNAs can rapidly regulate the expression of large groups of proteins. The RNA binding protein TRA2B (SFRS10) plays well-established roles in developmentally regulated alternative splicing during Drosophila sexual differentiation. TRA2B is also essential for mammalian embryogenesis and is implicated in numerous human diseases. Precise regulation of alternative splicing is critical to the development and function of the central nervous system; however the requirements for specific splicing factors in neurogenesis are poorly understood. In this study we focus on the role of TRA2B in mammalian brain development. We show that, during murine cortical neurogenesis, TRA2B is expressed in both neural progenitors and cortical projection neurons. Using cortex-specific Tra2b mutant mice, we find that TRA2B depletion results in apoptosis of the neural progenitor cells as well as disorganization of the cortical plate. Thus, TRA2B is essential for proper development of the cerebral cortex.
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