Stress granules and Sec bodies: From Drosophila to mammalian cells

Abstract

Cells are constantly exposed to a variety of endogenous and exogenous stresses that could be harmful. To cope with stresses, cells are able to change their biophysical characteristics in such a way that they survive and adapt, at least for a short period of stress time, so they can thrive when the stress is relieved. One of those mechanisms is the coalescence of macromolecules in stress assemblies that are thought to protect the molecules from degradation. Stress assemblies are characterized as condensed structures that have liquid-like properties (or solid), are membraneless and are pro-survival. In this thesis, we focused on two stress assemblies, stress granules and Sec bodies in Drosophila S2 cells as well as mammalian INS-1 cells. The aim was to identify several aspects of both. First, we have shown that using RNA-editing is successfully able to identify stress granule RNA in Drosophila single S2 cells and neurons. The identification of stress granule RNA in single cells have never been performed before. Second, we have unraveled two novel pathways for Sec body formation in S2 cells. The first pathway is via salt salt-inducible kinases (SIKs) that are activated by high salt stress (NaCl). The second pathway is activation of IRE1, PERK and SIKs through a combination of moderate salt stress (NaCl) and amino-acid starvation. Finally, we have shown for the first time that mammalian INS-1 cells form Sec bodies. They are similar in kinetics, dynamics and content as S2 Sec bodies indicating that they are conserved.