Molecularly distinct cores coexist inside stress granules

Stress granules are membraneless organelles that form in eukaryotic cells after stress exposure. Stress granules are constituted by a stable core and a dynamic shell that establishes a liquid-liquid phase separation with the surrounding cytosol. The structure and assembly of stress granules and how different components contribute to their formation are not fully understood. Here, using super resolution and expansion microscopy, we find that the stress granule component UBAP2L and the core protein G3BP1 occupy different domains inside stress granules. Since UBAP2L displays typical properties of a core protein, our results indicate that different cores coexist inside the same granule. Consistent with a role as a core protein, UBAP2L is required for stress granule assembly in several stress conditions and reverse genetics show that it acts upstream of G3BP1. We propose a model in which UBAP2L is an essential stress granule nucleator that facilitates G3BP1 core formation and stress granule assembly and growth.