The long non-coding RNA mimi scaffolds neuronal granules to maintain nervous system maturity. The long non-coding RNA mimi scaffolds neuronal granules to maintain nervous system maturity

RNA-binding proteins and messenger RNAs assemble into ribonucleoprotein granules that regulate mRNA trafficking, local translation, and turnover. The dysregulation of RNA-protein condensation disturbs synaptic plasticity and neuron survival, and has been widely associated with human neurological disease. Neuronal granules are thought to condense around particular proteins that dictate the identity and composition of each granule type. Here, we show in Drosophila that a previously uncharacterized long non-coding RNA, mimi, is required to scaffold large neuronal granules in the adult nervous system. Neuronal ELAV-like proteins directly bind mimi and mediate granule assembly, while Staufen maintains condensate integrity. mimi granules contain mRNAs and proteins involved in synaptic processes; granule loss in mimi mutant flies impairs nervous system maturity, neuropeptide-mediated signaling and causes phenotypes of neurodegeneration. Our work reports the first architectural RNA for a neuronal granule and provides a handle to interrogate functions of a condensate independently from those of its constituent proteins. Overall design: mRNA seq of wild-type (CantonS) flies

RNA结合蛋白（RNA-binding proteins）与信使RNA（messenger RNAs）组装形成核糖核蛋白颗粒（ribonucleoprotein granules），这类颗粒可调控mRNA的转运、局部翻译与降解。RNA-蛋白凝聚失调会扰乱突触可塑性与神经元存活，且已被广泛证实与人类神经系统疾病相关。学界普遍认为，神经元颗粒会围绕特定蛋白质凝聚，这些蛋白质决定了各类颗粒的特性与组成。本研究在果蝇（Drosophila）中发现，一种此前未被表征的长链非编码RNA（long non-coding RNA）mimi，可作为支架构建成体神经系统中的大型神经元颗粒。神经元ELAV样蛋白可直接结合mimi并介导颗粒组装，而Staufen则维持凝聚体的完整性。mimi颗粒含有参与突触过程的mRNA与蛋白质；mimi突变果蝇中的颗粒缺失会损害神经系统成熟、神经肽介导的信号传导，并引发神经退行性表型。本研究首次报道了神经元颗粒的结构性RNA，并为独立于其组成蛋白来研究凝聚体功能提供了研究抓手。整体实验设计：野生型（CantonS）果蝇的mRNA测序。