The ubiquitin ligase Hecw controls oogenesis and neuronal homeostasis by promoting the liquid state of ribonucleoprotein particles

Specialised ribonucleoprotein (RNP) granules are a hallmark of germ cells. Among their main function is the spatial and temporal modulation ofthe activity of specific mRNA transcripts that allow specification of primary embryonic axes. While RNPs composition and role are well established, their regulation is poorly defined. Here, we demonstrate that Hecw, a newly identified Drosophila ubiquitin ligase, is a key modulator of RNPs in oogenesis. Loss of Hecw activity results in the formation of enlarged granules that transition from a liquid to a gel-like state. At the molecular level, Hecw depletion leads to reduced ubiquitination and activity of the translational repressorFmrp, resultinginprematureOrbexpression/recruitmentinnursecells. In addition to defective oogenesis, flies lacking Hecw show neurodegenerative traits with prematureagingandclimbingdefectsduetoneuronalloss thatarelinkedtoRNPscondensation. Our findings reveal an unprecedented function of ubiquitin in modulating RNP fluidity and activity.