ROLE OF ELAV IN NEURONAL RNA PROCESSING

ELAV 在神经元 RNA 加工中的作用

• 批准号: 6687590
• 负责人: KALPANA P WHITE
• 金额: $ 23.71万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-10 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6687590
• 关键词: DNA; Drosophilidae; RNA binding protein; gene expression; immunoprecipitation; intermolecular interaction; messenger RNA; microarray technology; neurogenesis; neurons; posttranscriptional RNA processing; protein structure function; ribonucleoproteins

DESCRIPTION (provided by applicant): The long-term goal of this research project is to understand how differentially-expressed trans-acting factors in neurons can control pre-mRNA processing to precisely regulate neuronal gene expression. The powerful genetics, molecular biology and transgenic techniques of Drosophila, along with the emergent DNA microarray technology, will be utilized to study the role of ELAV in mRNA processing and its overall impact on gene expression in neurons. ELAV is the founding member of the ELAV/Hu family of RNA-binding proteins, which is conserved in both vertebrates and invertebrates. Members of the ELAV/Hu family serve diverse roles in mRNA processing, including splicing, stability and translatability. The aims of the project are: (1) elucidation of mechanisms of ELAV's interactions with RNA transcripts, (2) identification of direct targets of ELAV using immunoprecipitated ELAV-ribnucleoprotein complexes and DNA microarrays, (3) assessment of the overall impact of ELAV on gene expression using microarray technology. Together, these approaches will begin to identify networks of genes that are regulated collectively and provide a comprehensive view of how post-transcriptional regulation is utilized in neuronal gene expression. Given the evolutionary conservation between Drosophila and human genomes, insights in regulatory strategies will be directly transferable to human studies. Human members of the ELAV/Hu family have been implicated in pathogenesis of paraneoplastic cerebellar dysfunction. RNA processing defects have been documented in a large number of human diseases and inherited disorders including cancer, muscular dystrophy and fragile X syndrome.

描述（申请人提供）：本研究项目的长期目标是了解神经元中差异表达的反式作用因子如何控制前体mRNA加工，从而精确调节神经元基因表达。果蝇强大的遗传学、分子生物学和转基因技术，以及新兴的 DNA 微阵列技术，将被用来研究 ELAV 在 mRNA 加工中的作用及其对神经元基因表达的总体影响。 ELAV 是 RNA 结合蛋白 ELAV/Hu 家族的创始成员，该蛋白在脊椎动物和无脊椎动物中都是保守的。 ELAV/Hu 家族成员在 mRNA 加工中发挥多种作用，包括剪接、稳定性和可翻译性。该项目的目标是：(1) 阐明 ELAV 与 RNA 转录本相互作用的机制，(2) 使用免疫沉淀的 ELAV-核蛋白复合物和 DNA 微阵列鉴定 ELAV 的直接靶标，(3) 使用微阵列技术评估 ELAV 对基因表达的总体影响。总之，这些方法将开始识别共同调控的基因网络，并提供如何在神经元基因表达中利用转录后调控的全面视图。鉴于果蝇和人类基因组之间的进化保守性，监管方面的见解 策略将直接转移到人类研究中。 ELAV/Hu 家族的人类成员与副肿瘤性小脑功能障碍的发病机制有关。 RNA 加工缺陷已被记录在许多人类疾病和遗传性疾病中，包括癌症、肌肉萎缩症和脆性 X 综合征。