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Westerich, Kim Joana; Tarbashevich, Katsiaryna; Schick, Jan; Gupta, Antra; Zhu, Mingzhao; Hull, Kenneth; Romo, Daniel; Zeuschner, Dagmar; Goudarzi, Mohammad; Gross-Thebing, Theresa; Raz, Erez
Developmental cell, 09/2023, Letnik: 58, Številka: 17Journal Article
Germ granules, condensates of phase-separated RNA and protein, are organelles that are essential for germline development in different organisms. The patterning of the granules and their relevance for germ cell fate are not fully understood. 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 localization of RNA molecules to the periphery of the granules, where ribosomes are localized, depends on translational activity at this location. In addition, we find that the vertebrate-specific Dead end (Dnd1) protein is essential for nanos3 RNA localization at the condensates’ periphery. Accordingly, in the absence of Dnd1, or when translation is inhibited, nanos3 RNA translocates into the granule interior, away from the ribosomes, a process that is correlated with the loss of germ cell fate. These findings highlight the relevance of sub-granule compartmentalization for post-transcriptional control and its importance for preserving germ cell totipotency. Display omitted •The border of phase-separated germ granules is enriched with ribosomes•The presence of mRNAs at the granule periphery depends on their translational activity•Localization of nanos3 mRNA to the granule border requires Dnd1 function•Inhibition of nanos3 RNA translation leads to the loss of germ cell fate Westerich et al. study the distribution of RNA molecules within phase-separated organelles. They find that the presence of mRNAs at the periphery of germ cell granules requires RNA translation and interaction with specific RNA-binding proteins, and they show that mislocalization of RNAs is correlated with loss of germ cell fate.
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