CIS-ACTING SIGNALS AND TRANS-ACTING PROTEINS ARE INVOLVED IN TAU MESSENGER-RNA TARGETING INTO NEURITES OF DIFFERENTIATING NEURONAL CELLS
CIS-ACTING SIGNALS AND TRANS-ACTING PROTEINS ARE INVOLVED IN TAU MESSENGER-RNA TARGETING INTO NEURITES OF DIFFERENTIATING NEURONAL CELLS
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DOI：
10.1016/0736-5748(95)00001-w
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发表时间：
1995-04-01
影响因子：
1.8
通讯作者：
GINZBURG, I
中科院分区：
文献类型：
--
作者：
BEHAR, L;MARX, R;GINZBURG, I
Tau微管相关蛋白（Tau microtubule-associated protein，TAU）是一种神经元特异性蛋白，主要存在于轴突中，受发育调控，其功能是稳定微管，对神经元形态的建立和维持起重要作用。tau的轴突定位涉及在分化原代神经元培养中研究的多步骤过程。最初的步骤包括将其编码mRNA分选和亚细胞定位到轴突的近端部分。使用神经元细胞的转染试验，我们已经证明位于3'-非翻译区的序列包括参与tau mRNA靶向的顺式作用信号。此外，使用紫外交联测定，鉴定了43和38 kDa的两种RNA结合蛋白，其表现出与位于相同功能区域内的91个核苷酸的最小序列的特异性结合，这参与靶向。43和38-kDa的RNA结合蛋白存在于细胞质提取物中，从神经元细胞制备，并在分离的微管制剂，我们的研究结果支持一种新的模型，其中顺式作用信号，连同RNA结合蛋白，参与靶向tau mRNA，这可能最终导致其轴突定位。
Tau microtubule-associated protein is a neuron specific protein found primarily in axons and is developmentally regulated, The function of tau is in stabilization of microtubules, which is important in establishing and maintaining neuronal morphology. Axonal localization of tau involves a multistep process which is studied in differentiating primary neuronal culture. The initial step involves sorting and subcellular localization of its encoding mRNA into the proximal portion of the axon. Using the transfection assay into neuronal cells, we have demonstrated that sequences located in the 3'-untranslated region include a cis-acting signal which is involved in tau mRNA targeting. In addition, using ultraviolet cross-linking assay, two RNA-binding proteins of 43 and 38 kDa were identified, that exhibit specific binding to a minimal sequence of 91 nucleotides located within the same functional region, which is involved in targeting. The 43 and 38-kDa RNA-binding proteins are present in cytoplasmic extracts, prepared from neuronal cells, and in isolated microtubule preparations, Our results support a novel model in which cis-acting signals, together with RNA-binding proteins, are involved in the targeting of tau mRNA, that may ultimately lead to its axonal localization.