Patterning of phase-separated condensates by Dnd1 controls cell fate

SUMMARY Germ granules, condensates of phase-separated RNA and protein, are essential for germline development, but how these molecules are organized within the granules and whether such an organization is relevant for germ cell fate is unclear. Combining three-dimensional in vivo structural and functional analyses, we study the dynamic spatial organization of molecules within zebrafish germ granules. We find that the vertebrate-specific Dead end protein is essential for positioning nanos3 RNA at the condensates’ periphery, where ribosomes are located. Without Dead end, or when translation is inhibited, nanos3 RNA translocates into granule interiors, far from the ribosomes’ location. These findings reveal the molecular mechanisms controlling the spatial organization of RNA within the phase-separated organelle and the importance of subgranule RNA localization for preserving germ cell totipotency.