Tyramine induces dynamic RNP granule remodeling and translation activation in the Drosophila brain
Elife. 2021 Apr 23;10:e65742. doi: 10.7554/eLife.65742.
Nadia Formicola 1, Marjorie Heim 1, Jérémy Dufourt 2, Anne-Sophie Lancelot 1, Akira Nakamura 3, Mounia Lagha 2, Florence Besse 1
1 Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose, Nice, France.
2 Institut de Génétique Moléculaire de Montpellier, University of Montpellier, Montpellier, France.
3 Department of Germline Development, Institute of Molecular Embryology and Genetics, and Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
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.