Polar Positioning of Phase-Separated Liquid Compartments in Cells Regulated by an mRNA Competition Mechanism.
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.
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Shambaditya
S
Saha
Max Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany.
Christoph A
CA
Weber
Martin Luther University, 06120 Halle (Saale), Germany.
Marco
M
Nousch
Max Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany.
Omar
O
Adame-Arana
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Carsten
C
Hoege
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Marco Y
MY
Hein
Colorado State University, Fort Collins, CO 80523, USA.
Erin
E
Osborne-Nishimura
Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
Julia
J
Mahamid
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Marcus
M
Jahnel
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; Max Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany.
Louise
L
Jawerth
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Andrej
A
Pozniakovski
Martin Luther University, 06120 Halle (Saale), Germany.
Christian R
CR
Eckmann
Max Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany. Electronic address: julicher@pks.mpg.de.
Frank
F
Jülicher
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany. Electronic address: hyman@mpi-cbg.de.
Anthony A
AA
Hyman
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000378:metabolism; D016764:Cell Polarity; D004625:Embryo, Nonmammalian; D042541:Intracellular Space / Q000737:chemistry / Q000378:metabolism; D008962:Models, Theoretical; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000032:analysis / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C410587:MEX-5 protein, C elegans; C534959:PGL-3 protein, C elegans; D012333:RNA, Messenger; D016601:RNA-Binding Proteins