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（由申请人提供）：该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MRNA处理以精确调节神经元基因表达。果蝇的强大遗传学，分子生物学和转基因技术以及新兴的DNA微阵列技术将用于研究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结合蛋白的Elav/Hu家族的创始成员，该家族在脊椎动物和无脊椎动物中都是保守的。 Elav/Hu家族的成员在mRNA加工中起多种作用，包括剪接，稳定性和转换性。该项目的目的是：（1）阐明Elav与RNA转录物相互作用的机制，（2）使用免疫沉淀的Elav-核糖核蛋白复合物和DNA微阵列鉴定ELAV的直接靶标，（3）（3）使用微挤压技术评估Elav对基因表达的总体影响。总之，这些方法将开始识别受调节的基因网络，并提供有关在神经元基因表达中如何利用转录后调控的全面观点。鉴于果蝇和人类基因组之间的进化保守性，对调节的见解 策略将直接转移到人类研究中。 Elav/Hu家族的人类成员与副塑性小脑功能障碍的发病机理有关。 RNA处理缺陷已记录在大量的人类疾病和遗传性疾病中，包括癌症，肌肉营养不良和脆弱的X综合征。