Upon cellular stress, translation is terminated and mRNAs are captured in processing bodies (P-bodies) – membraneless organelles that represent either storage or decay compartments depending on the individual mRNA. Phase separation of some components, such as the helicase Dhh1, has been proposed to contribute to P-body assembly, but the regulation of this process is not well understood. In this study, Kiril Tishinov and Anne Spang (Tishinov and Spang, 2021) now analyse the role of the translational repressor Scd6 and the decapping stimulator Edc3 in P-body assembly in yeast using edc3Δ scd6Δ double mutants. They found that in these cells, P-body formation is blocked, and Dcp1 and Dcp2, subunits of decapping complex, are actively transported to and accumulate in the nucleus. However, this does not result in nuclear mRNA decay, suggesting that the nuclear decapping complex acts a reservoir and that mRNA decay occurs in the cytoplasm. Furthermore, the authors show that P-body assembly is initiated by Dcp2 and mostly occurs at the ER, not randomly in the cytoplasm as has been assumed previously. Finally, they provide evidence that Edc3 can bridge Dcp2 to Dhh1, thereby facilitating phase separation and P-body formation. This work thus presents a novel means for the regulation of P-body assembly, and it will be interesting to investigate whether this pathway is conserved in mammalian cells.
