Project description: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.
Project description: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.
Project description: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.
Project description: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.
Project description:In neurons, mRNAs and associated RNA-binding proteins assemble into ribonucleoprotein (RNP) granules essential to regulate mRNA trafficking, local translation, and turnover. Dysregulation of RNA-protein condensation can disturb synaptic plasticity. We report that the novel lncRNA mimi is a constitutive and essential component of large cytoplasmic condensates (RNP granules) in fly neurons. In order to identify direct mimi RNA binders we employ RAP assisted purification of mimi RNPs subsequent to UV-crosslinking of adult fly brain tissue (non UV irradiated samples serve as control). Applying relative Max Quant LFQ quantification (Max LFQ) we carry out a differential proteomic analysis of mimi RNP complexes in UV-irradiated versus non irradiated fly brains.