A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators.
A nuclear function of Hu proteins as neuron-specific alternative RNA processing regulators.
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DOI：
10.1091/mbc.e06-02-0099
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发表时间：
2006-12
影响因子：
3.3
通讯作者：
Hui-Ming Zhu;Robert A. Hasman;Victoria A Barron;G. Luo;H. Lou
中科院分区：
文献类型：
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作者：
Hui-Ming Zhu;Robert A. Hasman;Victoria A Barron;G. Luo;H. Lou
选择性剪接的全基因组分析的最新进展表明，广泛的选择性RNA加工与许多在神经系统中发挥重要作用的蛋白质有关。虽然差异剪接和多聚腺苷酸化对神经系统的复杂性做出了重要贡献，但我们对神经元特异性通路的调控机制的理解非常有限。哺乳动物神经元特异性胚胎致死异常视觉样Hu蛋白（HuB、HuC和HuD）是一个与神经元分化和维持有关的RNA结合蛋白家族。已经确定，Hu蛋白通过上调细胞质中的mRNA稳定性和/或翻译来增加与神经元功能相关的蛋白质的表达。我们在这里报告了一个新的功能，这些蛋白质作为RNA加工调节器在细胞核中。我们进一步阐明了这种调节的潜在机制。我们发现，在神经元样细胞中，胡蛋白阻断TIA-1/TIAR的活性，TIA-1/TIAR是两种先前鉴定的普遍表达的蛋白质，它们促进降钙素/降钙素基因相关肽（CGRP）前mRNA加工的非神经元途径。这些研究不仅定义了降钙素/CGRP系统的第一个神经元特异性调节因子，而且还定义了Hu蛋白的第一个核功能。
Recent advances in genome-wide analysis of alternative splicing indicate that extensive alternative RNA processing is associated with many proteins that play important roles in the nervous system. Although differential splicing and polyadenylation make significant contributions to the complexity of the nervous system, our understanding of the regulatory mechanisms underlying the neuron-specific pathways is very limited. Mammalian neuron-specific embryonic lethal abnormal visual-like Hu proteins (HuB, HuC, and HuD) are a family of RNA-binding proteins implicated in neuronal differentiation and maintenance. It has been established that Hu proteins increase expression of proteins associated with neuronal function by up-regulating mRNA stability and/or translation in the cytoplasm. We report here a novel function of these proteins as RNA processing regulators in the nucleus. We further elucidate the underlying mechanism of this regulation. We show that in neuron-like cells, Hu proteins block the activity of TIA-1/TIAR, two previously identified, ubiquitously expressed proteins that promote the nonneuronal pathway of calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA processing. These studies define not only the first neuron-specific regulator of the calcitonin/CGRP system but also the first nuclear function of Hu proteins.