Abstract
Prion-like domains (PLDs), defined by their low sequence complexity and intrinsic disorder, are present in hundreds of human proteins. Although gain-of-function mutations in the PLDs of neuronal RNA-binding proteins have been linked to neurodegenerative disease progression, the physiological role of PLDs and their range of molecular functions are still largely unknown. Here, we show that the PLD of Drosophila Imp, a conserved component of neuronal ribonucleoprotein (RNP) granules, is essential for the developmentally-controlled localization of Imp RNP granules to axons and regulates in vivo axonal remodeling. Furthermore, we demonstrate that Imp PLD restricts, rather than promotes, granule assembly, revealing a novel modulatory function for PLDs in RNP granule homeostasis. Swapping the position of Imp PLD compromises RNP granule dynamic assembly but not transport, suggesting that these two functions are uncoupled. Together, our study uncovers a physiological function for PLDs in the spatio-temporal control of neuronal RNP assemblies.
Highlights
Prion-like domains (PLDs), defined by their low sequence complexity and intrinsic disorder, are present in hundreds of human proteins
We have explored the role of a PLD found in Drosophila Imp, a known component of neuronal RNP granules belonging to the conserved family of VICKZ RNA-binding proteins
G080-GFPImp-CRISPR-ΔPLD homozygous flies, in contrast to flies lacking the function of imp[47], were homozygous viable and fertile, suggesting that Imp PLD is not required to support the essential functions of the Imp protein
Summary
Prion-like domains (PLDs), defined by their low sequence complexity and intrinsic disorder, are present in hundreds of human proteins. Cytoplasmic RNP granules of different sizes, composition, and properties have been defined over the last past decades, including large macromolecular complexes such as P-bodies, stress granules, germ cell granules or neuronal granules[2] These assemblies are enriched in helicases, regulators of mRNA translation and stability, and/or molecular motors. We have explored the role of a PLD found in Drosophila Imp, a known component of neuronal RNP granules belonging to the conserved family of VICKZ RNA-binding proteins In both vertebrate and invertebrate neurons, Imp family members are packaged together with target mRNAs into microscopically visible granules that are transported to the axons and/or dendrites of neuronal cells[36,37,38,39]. By uncovering an unexpected function of a PLD in RNP granule homeostasis, they shed new light into the molecular principles and requirements underlying RNP granule assembly and regulation in living cells
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