FUNCTIONS OF HNRNP A1 AND PTB IN THE CYTOPLASM

HNRNP A1 和 PTB 在细胞质中的功能

• 批准号: 6170329
• 负责人: STEPHANIE T SHI
• 金额: $ 2.46万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6170329
• 关键词: RNA binding protein; RNA splicing; cytoplasm; genetic transcription; genetic translation; heterogeneous nuclear ribonucleoprotein; murine hepatitis virus; protein structure function; virus RNA; virus genetics

DESCRIPTION There are several RNA-binding proteins, including heterogeneous nuclear ribonucleoprotein (hnRNP A1) and polypyrimidine tract-binding protein (PTB/hnRNP 1), that were initially characterized as nuclear proteins but later found to shuttle between the nucleus and the cytoplasm. These proteins play important roles in RNA splicing shown to interact with RNAs of several RNA viruses including mouse hepatitis virus (MHV), and may possibly be involved in viral RNA transcription and translation in the cytoplasm. It has been hypothesized that the discontinuous transcription of MHV RNA may involve RNA splicing, a function that has never been thought to be present in the cytoplasm before. As nuclear splicing factors, hnRNP A1 and PTB may possess similar functions in the cytoplasm. Thus, the purpose of this proposal is to study the potential roles in splicing of these proteins in the cytoplasm using MHV as a model systems. I will first establish the functional importance of hnRNP A1 and PTB in MHV RNA transcription by immunodepletion of these proteins in an in vitro transcription system. I will then focus my study on the possible cytoplasmic RNA splicing as a mechanism by which hnRNP A1 and PTB regulate MHV RNA transcription. Finally, I will also investigate the effects of PTB and hnRNP A1 and PTB regulate MHV RNA transcription. Finally, I will also investigate the effects of PTB and hnRNP A1 on MHV protein translation. By the completion of the proposed studies, I hope to characterize the functions of hnRNP A1 and PTB in the cytoplasm of MHV-infected cells, which may reflect their normal cytoplasmic functions.

描述 有几种 RNA 结合蛋白，包括异质核核糖核蛋白 (hnRNP A1) 和多聚嘧啶束结合蛋白 (PTB/hnRNP 1)，最初被定性为核蛋白，但后来发现它们在细胞核和细胞质之间穿梭。这些蛋白质在 RNA 剪接中发挥重要作用，可与包括小鼠肝炎病毒 (MHV) 在内的多种 RNA 病毒的 RNA 相互作用，并且可能参与病毒 RNA 在细胞质中的转录和翻译。据推测，MHV RNA 的不连续转录可能涉及 RNA 剪接，这是一种以前从未被认为存在于细胞质中的功能。作为核剪接因子，hnRNP A1 和 PTB 在细胞质中可能具有相似的功能。因此，本提案的目的是使用 MHV 作为模型系统来研究这些蛋白质在细胞质中剪接的潜在作用。我将首先通过在体外转录系统中免疫耗竭这些蛋白质来确定 hnRNP A1 和 PTB 在 MHV RNA 转录中的功能重要性。然后我将集中研究可能的细胞质 RNA 剪接作为 hnRNP A1 和 PTB 调节 MHV RNA 转录的机制。最后，我还将研究PTB和hnRNP A1和PTB调节MHV RNA转录的作用。最后，我还将研究 PTB 和 hnRNP A1 对 MHV 蛋白翻译的影响。通过完成拟议的研究，我希望能够表征 MHV 感染细胞细胞质中 hnRNP A1 和 PTB 的功能，这可能反映其正常的细胞质功能。