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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nontelomeric splice variant of telomere repeat-binding factor 2 maintains neuronal traits by sequestering repressor element 1-silencing transcription factor
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Nontelomeric splice variant of telomere repeat-binding factor 2 maintains neuronal traits by sequestering repressor element 1-silencing transcription factor

机译：端粒重复结合因子2的非端粒剪接变体通过隔离阻遏物1-沉默转录因子来维持神经元性状

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摘要

Telomere repeat-binding factor 2 (TRF2) is critical for telomere integrity in dividing stem and somatic cells, but its role in postmitotic neurons is unknown. Apart from protecting telomeres, nuclear TRF2 interacts with the master neuronal gene-silencer repressor element 1-silencing transcription factor (REST), and disruption of this interaction induces neuronal differentiation. Here we report a developmental switch from the expression of TRF2 in proliferating neural progenitor cells to expression of a unique short nontelomeric iso-form of TRF2 (TRF2-S) as neurons establish a fully differentiated state. Unlike nuclear TRF2, which enhances REST-mediated gene repression, TRF2-S is located in the cytoplasm where it sequesters REST, thereby maintaining the expression of neuronal genes, including those encoding glutamate receptors, cell adhesion, and neuro-filament proteins. In neurons, TRF2-S-mediated antagonism of REST nuclear activity is greatly attenuated by either overexpression of TRF2 or administration of the excitatory amino acid kainic acid. Overexpression of TRF2-S rescues kainic acid-induced REST nuclear accumulation and its gene-silencing effects. Thus, TRF2-S acts as part of a unique developmentally regulated molecular switch that plays critical roles in the maintenance and plasticity of neurons.
机译：端粒重复结合因子2（TRF2）在分裂干细胞和体细胞中对于端粒完整性至关重要，但其在有丝分裂后神经元中的作用尚不清楚。除了保护端粒外，核TRF2还与主神经元基因沉默子阻遏元件1沉默转录因子（REST）相互作用，并且这种相互作用的破坏会诱导神经元分化。在这里，我们报道了神经细胞建立完全分化状态后，TRF2在增殖的神经祖细胞中的表达向TRF2的独特短非端粒异构形式（TRF2-S）的表达转变。不同于增强REST介导的基因阻抑的核TRF2，TRF2-S位于细胞质中，它隔离REST，从而维持神经元基因的表达，包括编码谷氨酸受体，细胞粘附和神经丝蛋白的基因。在神经元中，TRF2的过表达或兴奋性氨基酸红藻氨酸的施用大大减轻了TRF2-S介导的REST核活性拮抗作用。 TRF2-S的过表达可以拯救海藻酸诱导的REST核积累及其基因沉默效应。因此，TRF2-S充当独特的受发育调节的分子开关的一部分，该开关在神经元的维持和可塑性中起关键作用。

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  • 作者

    Peisu Zhang; Rebecca Casaday-Potts; Patricia Precht; Haiyang Jiang; Yie Liu; Michael J. Pazin; Mark P. Mattson;

  • 作者单位

    Laboratories of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224;

    Laboratories of Cellular and Molecular Biology, National Institute on Aging Intramural Research Program, Baltimore, MD 21224;

    Laboratories of Cellular and Molecular Biology, National Institute on Aging Intramural Research Program, Baltimore, MD 21224;

    Laboratories of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224;

    Laboratories of Molecular Gerontology, National Institute on Aging Intramural Research Program, Baltimore, MD 21224;

    Laboratories of Cellular and Molecular Biology, National Institute on Aging Intramural Research Program, Baltimore, MD 21224;

    Laboratories of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD 21224;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    brain development; RE1 element; cajal-retzius cells; alternative splicing; proteasomal degradation;

    机译：大脑发育;RE1元素;cajal-retzius细胞;替代拼接;蛋白酶体降解;

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