Neuronal RNA-binding proteins in mRNA localization

mRNA 定位中的神经元 RNA 结合蛋白

• 批准号: 282896774
• 负责人: Professor Dr. Dierk Niessing
• 金额: --
• 依托单位: Institut für Pharmazeutische Biotechnologie
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/282896774?language=en
• 关键词: Neuronal; RNA; binding; proteins; mRNA

The double-stranded RNA-binding protein (dsRBP) Staufen2 (Stau2) critically contributes to the transport of mRNAs to dendrites of polarized neurons. Recently, we have identified the first set of physiological RNA targets of Stau2, including the regulator of small G protein signaling (Rgs4) mRNA, which is implicated in neuropsychiatric disorders. In this project, we wish to understand how Stau2 binds specifically to Rgs4 mRNA and what the implications for this transcript are. Stau2 together with the RBP Pumilio2 (Pum2) are part of RNA granules in mammalian neurons. Preliminary evidence indicates that both RBPs may functionally and physically interact with each other. Furthermore, Stau2 protein is significantly down-regulated in both Pum2-deficient neurons as well as in Pum2-deficient mice. The goal of this project is to study the mechanistic basis and functional implications of Stau2 binding to Rgs4 mRNA and the contribution of Pum2 to Stau2-mediated RNA binding. Our aim is to understand how Rgs4 mRNA is specifically recognized by Stau2 and what implications this has for Rgs4 transcript stability and localization.

双链RNA结合蛋白(DsRBP)Staufen2(Stau2)在mRNAs向极化神经元树突的运输中起重要作用。最近，我们已经确定了Stau2的第一组生理RNA靶点，包括与神经精神障碍有关的小G蛋白信号转导调节因子(RGS4)mRNA。在这个项目中，我们希望了解Stau2是如何与RGS4 mRNA特异性结合的，以及对这个转录本的影响是什么。Stau2和RBP Pumilio2(Pum2)是哺乳动物神经元中RNA颗粒的一部分。初步证据表明，这两种限制性商业惯例可以在功能和物理上相互作用。此外，在Pum2缺陷的神经元和Pum2缺陷的小鼠中，Stau2蛋白都显著下调。本项目的目的是研究Stau2与RGS4mRNA结合的机制基础和功能意义，以及Pum2在Stau2介导的RNA结合中的作用。我们的目的是了解RGS4 mRNA是如何被Stau2特异性识别的，以及这对RGS4转录本的稳定性和定位有什么影响。