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异质核核糖核蛋白 F 是少突胶质细胞 RNA 运输颗粒的一个新成分,有助于髓鞘碱性蛋白 (MBP) 合成的调节。

Heterogeneous nuclear ribonucleoprotein (hnRNP) F is a novel component of oligodendroglial RNA transport granules contributing to regulation of myelin basic protein (MBP) synthesis.

机构信息

Department of Biology, Molecular Cell Biology, Johannes Gutenberg University of Mainz, Bentzelweg 3, 55128 Mainz, Germany.

出版信息

J Biol Chem. 2012 Jan 13;287(3):1742-54. doi: 10.1074/jbc.M111.235010. Epub 2011 Nov 29.

Abstract

Myelin basic protein (MBP) is a major component of central nervous system (CNS) myelin. The absence of MBP results in the loss of almost all compact myelin in the CNS. MBP mRNA is sorted into RNA granules that are transported to the periphery of oligodendrocytes in a translationally inactive state. A central mediator of this transport process is the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 that binds to the cis-acting A2-response element in the 3'UTR of MBP mRNA. Recently, we found that activation of the Src family nonreceptor tyrosine kinase Fyn in oligodendrocytes leads to phosphorylation of hnRNP A2 and to increased translation of MBP mRNA. Here, we identify the RNA-binding protein hnRNP F as a novel component of MBP mRNA transport granules. It is associated with hnRNP A2 and MBP mRNA in cytoplasmic granular structures and is involved in post-transcriptional regulation of MBP expression. Fyn kinase activity results in phosphorylation of hnRNP F in the cytoplasm and its release from MBP mRNA and RNA granules. Our results define hnRNP F as a regulatory element of MBP expression in oligodendrocytes and imply an important function of hnRNP F in the control of myelin synthesis.

摘要

髓鞘碱性蛋白(MBP)是中枢神经系统(CNS)髓鞘的主要成分。MBP 的缺失导致 CNS 中几乎所有致密髓鞘的丧失。MBP mRNA 被分拣到 RNA 颗粒中,以翻译失活状态被运输到少突胶质细胞的外周。这种运输过程的中央介质是反式作用因子异质核核糖核蛋白(hnRNP)A2,它与 MBP mRNA 3'UTR 中的顺式作用 A2 反应元件结合。最近,我们发现少突胶质细胞中Src 家族非受体酪氨酸激酶 Fyn 的激活导致 hnRNP A2 的磷酸化,并增加 MBP mRNA 的翻译。在这里,我们确定 RNA 结合蛋白 hnRNP F 是 MBP mRNA 运输颗粒的一个新成分。它与 hnRNP A2 和 MBP mRNA 一起存在于细胞质颗粒结构中,并参与 MBP 表达的转录后调控。Fyn 激酶活性导致细胞质中 hnRNP F 的磷酸化及其从 MBP mRNA 和 RNA 颗粒中的释放。我们的结果将 hnRNP F 定义为少突胶质细胞中 MBP 表达的调节元件,并暗示 hnRNP F 在髓鞘合成控制中的重要功能。

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