GSE183812
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: totalRNAseq of FNE, RBP9 mutants and wild-type control. 5 replicates per genotype; 4 different genotypes: wild type (w1118), ?fne (fne?/fneKOZ2 (females) and fne? or fneKOZ2 (males)), ?rbp9 (rbp9P2690/Df(2L)ED206 (males and females)) and ?fne?rbp9 (fne?/fneKOZ2; rbp9P2690/Df(2L)ED206 (females) and fne?; rbp9P2690/ Df(2L)ED206 or fneKOZ2; rbp9P2690/Df(2L)ED206 (males))