ROLE OF RNAI IN ADULT MAMMALIAN BRAIN

RNAI 在成年哺乳动物大脑中的作用

• 批准号: 7358079
• 负责人: NEIL R SMALHEISER
• 金额: $ 0.61万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7358079
• 关键词: ROLE; RNAI; ADULT; MAMMALIAN; BRAIN

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have previously predicted that RNA interference (RNAi) may occur physiologically in the adult brain and participate in regulating gene expression changes involved in learning and memory. Since this prediction, a large number of microRNAs have been demonstrated to be present in adult brain, interact with fmr protein and might regulate protein synthesis. We want to learn if Dicer, EIF-2c and other proteins involved in RNAi are expressed at dendritic spines, and if they regulate local synthesis of specific microRNAs and mRNAs. At UIC we are carrying out biochemical and behavioral studies of this question, as well as trying to knock out Dicer in vivo. However, we seek to take advantage of the expertise of NCMIR in localizing Dicer and EIF-2c proteins morphologically, particularly during neuronal activation and learning. We also need to localize individual microRNAs, microRNA precursors and their mRNA targets at high resolution using in situ hybridization. Finally, we would like to look for dynamic changes in the association of Dicer with other proteins and RNAs using resonance energy transfer.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们此前预测，RNA干扰(RNAi)可能在成人大脑中生理性地发生，并参与调节涉及学习和记忆的基因表达变化。自从这一预测以来，大量的microRNAs已被证明存在于成人大脑中，与fmr蛋白相互作用，并可能调节蛋白质的合成。我们想知道DICER、EIF-2c和其他参与RNAi的蛋白质是否在树突上表达，以及它们是否调节特定microRNAs和mRNAs的局部合成。在UIC，我们正在对这个问题进行生化和行为研究，并试图在体内敲除迪格尔。然而，我们试图利用NCMIR的专业知识在形态上定位Dier和eIF-2c蛋白，特别是在神经元激活和学习期间。我们还需要使用原位杂交高分辨率地定位单个microRNAs、microRNA前体及其mRNA靶标。最后，我们希望通过共振能量转移来寻找DICER与其他蛋白质和RNA之间的联系的动态变化。