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Cell. 2016 Sep 8;166(6):1572-1584.e16. doi: 10.1016/j.cell.2016.08.006. Epub 2016 Sep 1.

Polar Positioning of Phase-Separated Liquid Compartments in Cells Regulated by an mRNA Competition Mechanism.

Author information

1
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
2
Max Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany.
3
Martin Luther University, 06120 Halle (Saale), Germany.
4
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
5
Colorado State University, Fort Collins, CO 80523, USA.
6
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany.
7
Max Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany. Electronic address: julicher@pks.mpg.de.
8
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Electronic address: hyman@mpi-cbg.de.

Abstract

P granules are non-membrane-bound RNA-protein compartments that are involved in germline development in C. elegans. They are liquids that condense at one end of the embryo by localized phase separation, driven by gradients of polarity proteins such as the mRNA-binding protein MEX-5. To probe how polarity proteins regulate phase separation, we combined biochemistry and theoretical modeling. We reconstitute P granule-like droplets in vitro using a single protein PGL-3. By combining in vitro reconstitution with measurements of intracellular concentrations, we show that competition between PGL-3 and MEX-5 for mRNA can regulate the formation of PGL-3 droplets. Using theory, we show that, in a MEX-5 gradient, this mRNA competition mechanism can drive a gradient of P granule assembly with similar spatial and temporal characteristics to P granule assembly in vivo. We conclude that gradients of polarity proteins can position RNP granules during development by using RNA competition to regulate local phase separation.

PMID:
27594427
PMCID:
PMC5034880
DOI:
10.1016/j.cell.2016.08.006
[Indexed for MEDLINE]
Free PMC Article

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