Abstract
Ribonucleoprotein (RNP) granules are dynamic condensates enriched in regulatory RNA binding proteins (RBPs) and RNAs under tight spatiotemporal control. Extensive recent work has investigated the molecular principles underlying RNP granule assembly, unraveling that they form through the self-association of RNP components into dynamic networks of interactions. How endogenous RNP granules respond to external stimuli to regulate RNA fate is still largely unknown. Here, we demonstrate through high-resolution imaging of intact Drosophila brains that Tyramine induces a reversible remodeling of somatic RNP granules characterized by the decondensation of granule-enriched RBPs (e.g. Imp/ZBP1/IGF2BP) and helicases (e.g. Me31B/DDX-6/Rck). Furthermore, our functional analysis reveals that Tyramine signals both through its receptor TyrR and through the calcium-activated kinase CamkII to trigger RNP component decondensation. Finally, we uncover that RNP granule remodeling is accompanied by the rapid and specific translational activation of associated mRNAs. Thus, this work sheds new light on the mechanisms controlling cue-induced rearrangement of physiological RNP condensates.
Highlights
Self-assembly of functionally related molecules into the so-called biological condensates has recently emerged as a prevalent process underlying subcellular compartmentalization (Alberti, 2017; Banani et al, 2017)
Through high resolution live imaging of intact brains, we show that this is characterized by the decondensation of two conserved components of RNP granules: the RNA binding proteins (RBPs) Imp/ZBP1/IGF2BP and the DEAD box helicase Me31B/DDX-6/Rck (Tiruchinapalli et al, 2003; Barbee et al, 2006; Miller et al, 2009; Hillebrand et al, 2010; Vijayakumar et al, 2019)
We show that RNP granule remodeling is linked to the translation activation of granule-associated mRNAs, a process we monitor with unprecedented resolution via the SunTag amplification system (Tanenbaum et al, 2014) recently implemented in Drosophila (Dufourt et al, 2021)
Summary
Self-assembly of functionally related molecules into the so-called biological condensates has recently emerged as a prevalent process underlying subcellular compartmentalization (Alberti, 2017; Banani et al, 2017). Any alteration in stoichiometry, valency, or binding affinity will dramatically impact on both scaffold condensation and recruitment of client molecules (Banani et al, 2016; Ditlev et al, 2018; Sanders et al, 2020) Because they modulate both protein–protein and protein–RNA interactions, post-translational modifications have in this context been shown to alter the phase behavior of RNA binding proteins (RBPs) in vitro, and to inhibit or promote their partitioning into endogenous condensates in a switch-like manner (Hofweber and Dormann, 2019; Snead and Gladfelter, 2019). By illustrating how the properties of these macromolecular assemblies can contribute to dynamic and specific regulation of neuronal mRNAs, this work opens new perspectives on the regulation and function of constitutive RNP condensate in physiological contexts
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