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Pat1 promotes processing body assembly by enhancing the phase separation of the DEAD-box ATPase Dhh1 and RNA.

eLife | 2019

Processing bodies (PBs) are cytoplasmic mRNP granules that assemble via liquid-liquid phase separation and are implicated in the decay or storage of mRNAs. How PB assembly is regulated in cells remains unclear. Previously, we identified the ATPase activity of the DEAD-box protein Dhh1 as a key regulator of PB dynamics and demonstrated that Not1, an activator of the Dhh1 ATPase and member of the CCR4-NOT deadenylase complex inhibits PB assembly in vivo (Mugler et al., 2016). Here, we show that the PB component Pat1 antagonizes Not1 and promotes PB assembly via its direct interaction with Dhh1. Intriguingly, in vivo PB dynamics can be recapitulated in vitro, since Pat1 enhances the phase separation of Dhh1 and RNA into liquid droplets, whereas Not1 reverses Pat1-Dhh1-RNA condensation. Overall, our results uncover a function of Pat1 in promoting the multimerization of Dhh1 on mRNA, thereby aiding the assembly of large multivalent mRNP granules that are PBs.

Pubmed ID: 30648970 RIS Download

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R01GM058065
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM101257
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM058065
  • Agency: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, International
    Id: 31003A_159731
  • Agency: ETH Zürich, International
    Id: FEL-37-14-2
  • Agency: NIGMS NIH HHS, United States
    Id: R01GM101257
  • Agency: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, International
    Id: 31003A_179275
  • Agency: Human Frontier Science Program, International
    Id: LT000914/2015

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