Abstract

Drosophila eggs are highly polarised cells that use RNA–protein complexes to regulate storage and translational control of maternal RNAs. Ribonucleoprotein granules are a class of biological condensates that form predominantly by intracellular phase separation. Despite extensive in vitro studies testing the physical principles regulating condensates, how phase separation translates to biological function remains largely unanswered. In this perspective, we discuss granules in Drosophila oogenesis as a model system for investigating the physiological role of phase separation. We review key maternal granules and their properties while highlighting ribonucleoprotein phase separation behaviours observed during development. Finally, we discuss how concepts and models from liquid–liquid phase separation could be used to test mechanisms underlying granule assembly, regulation and function in Drosophila oogenesis.

Highlights

  • Intracellular localisation of messenger RNAs is a conserved mechanism for achieving compartmentalised protein expression in polarised cells such as neurons and fibroblasts [1,2,3,4,5]

  • highly conserved biomolecular condensates involved in regulating RNA metabolism

  • • Studying the physicochemical principles of RNP granules in the Drosophila egg chamber could provide insights

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Summary

Introduction

Intracellular localisation of messenger RNAs (mRNAs) is a conserved mechanism for achieving compartmentalised protein expression in polarised cells such as neurons and fibroblasts [1,2,3,4,5]. According to the ‘scaffold and client’ model, scaffolds are essential proteins that help promote granule assembly, while clients are proteins that transiently interact with scaffolds and regulate condensate properties [91,92,93] While this model has primarily been explored in vitro, RNP granules in the developing egg are a powerful in vivo system to test the model and have the advantage of overlapping RBPs associated with different granules. Separate studies have demonstrated that RNAse treatment results in the breakdown of RNP granules, highlighting the importance of RNA in maintaining the integrity of RNP granules [66,78] These observations suggest a model whereby ‘sticky’ mRNAs promote granule nucleation by concentrating key scaffold proteins through sequence specific binding and subsequently regulate stability and material property. In vitro studies would be amenable to testing RNA sequences, for example in the untranslated regions, in the formation and regulation of RNP granules

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