Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg 79108, Germany.
Faculty of Biology, Albert Ludwig University of Freiburg, Freiburg 79104, Germany.
Sci Adv. 2022 Sep 30;8(39):eabo5578. doi: 10.1126/sciadv.abo5578. Epub 2022 Sep 28.
RNA binding proteins and messenger RNAs (mRNAs) 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 that a previously uncharacterized long noncoding RNA, , is required to scaffold large neuronal granules in the adult nervous system. Neuronal ELAV-like proteins directly bind and mediate granule assembly, while Staufen maintains condensate integrity. granules contain mRNAs and proteins involved in synaptic processes; granule loss in mutant flies impairs nervous system maturity and neuropeptide-mediated signaling and causes phenotypes of neurodegeneration. Our work reports an architectural RNA for a neuronal granule and provides a handle to interrogate functions of a condensate independently of those of its constituent proteins.
RNA 结合蛋白和信使 RNA(mRNA)组装成核糖核蛋白颗粒,调节 mRNA 的运输、局部翻译和周转。RNA-蛋白凝聚的失调扰乱了突触可塑性和神经元存活,并与人类神经疾病广泛相关。神经元颗粒被认为是围绕特定的蛋白质凝聚的,这些蛋白质决定了每个颗粒类型的身份和组成。在这里,我们在 中表明,以前未被表征的长非编码 RNA 是成年神经系统中大型神经元颗粒形成所必需的。神经元 ELAV 样蛋白直接结合 并介导颗粒组装,而 Staufen 则维持凝聚体的完整性。 颗粒包含参与突触过程的 mRNA 和蛋白质; 在 突变体果蝇中颗粒的缺失会损害神经系统的成熟和神经肽介导的信号传递,并导致神经退行性变的表型。我们的工作报告了一种神经元颗粒的结构 RNA,并提供了一个独立于凝聚体组成蛋白来研究凝聚体功能的方法。