Carson J H, Cui H, Krueger W, Schlepchenko B, Brumwell C, Barbarese E
Department of Biochemistry, University of Connecticut Health Center, Farmington, CT 06030, USA.
Results Probl Cell Differ. 2001;34:69-81. doi: 10.1007/978-3-540-40025-7_5.
A2RE and hnRNP A2 have been identified as important cis/trans determinants for MBP RNA trafficking in oligodendrocytes. Since A2RE-like sequences are found in several different transported RNAs, and since hnRNP A2 is expressed in most cell types, this may represent a general RNA trafficking pathway shared by a variety of different RNAs in different cell types. In oligodendrocytes, A2RE/hnRNP A2 determinants are involved in at least four steps in the RNA trafficking pathway: (1) export from the nucleus to the cytoplasm, (2) granule assembly in the perikaryon, (3) transport along microtubules in the processes, and (4) translation activation in the myelin compartment. The components of the cellular machinery mediating each of these steps are known. How A2RE/hnRNP A2 determinants interact with these components to mediate RNA trafficking is being investigated by a combination of: biochemistry to analyze molecular interactions in vitro, imaging to visualize molecular interactions in living cells, and computational modeling to simulate molecular interactions in the Virtual Cell.
A2RE和hnRNP A2已被确定为少突胶质细胞中MBP RNA转运的重要顺式/反式决定因素。由于在几种不同的转运RNA中发现了类似A2RE的序列，并且由于hnRNP A2在大多数细胞类型中都有表达，这可能代表了不同细胞类型中多种不同RNA共享的一种通用RNA转运途径。在少突胶质细胞中，A2RE/hnRNP A2决定因素参与RNA转运途径的至少四个步骤：（1）从细胞核输出到细胞质，（2）在核周颗粒组装，（3）在突起中沿微管运输，以及（4）在髓鞘区室中的翻译激活。介导这些步骤中每一步的细胞机制的组成部分是已知的。目前正在通过以下组合研究A2RE/hnRNP A2决定因素如何与这些组成部分相互作用以介导RNA转运：生物化学分析体外分子相互作用、成像观察活细胞中的分子相互作用以及计算建模模拟虚拟细胞中的分子相互作用。
