A Molecular Grammar Governing the Driving Forces for Phase Separation of 
Prion-like RNA Binding Proteins.

Wang, Jie; Choi, Jeong-Mo; Holehouse, Alex S; Lee, Hyun O.; Zhang, Xiaojie; Jahnel, Marcus; Maharana, Shovamayee; Lemaitre, Regis P.; Pozniakovsky, Andrei I.; Drechsel, David N.; Poser, Ina; Pappu, Rohit V; Alberti, Simon; Hyman, Anthony

doi:10.1016/j.cell.2018.06.006

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A Molecular Grammar Governing the Driving Forces for Phase Separation of Prion-like RNA Binding Proteins.

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/persons/resource/persons222397

Wang, Jie
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219377

Lee, Hyun O.
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons204000

Jahnel, Marcus
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219414

Maharana, Shovamayee
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219380

Lemaitre, Regis P.
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219547

Pozniakovsky, Andrei I.
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219118

Drechsel, David N.
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219545

Poser, Ina
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons218962

Alberti, Simon
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219253

Hyman, Anthony
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Citation

Wang, J., Choi, J.-M., Holehouse, A. S., Lee, H. O., Zhang, X., Jahnel, M., et al. (2018). A Molecular Grammar Governing the Driving Forces for Phase Separation of Prion-like RNA Binding Proteins. Cell, 174(3), 688-699. doi:10.1016/j.cell.2018.06.006.

Cite as: https://hdl.handle.net/21.11116/0000-0003-F6B9-7

Abstract

Proteins such as FUS phase separate to form liquid-like condensates that can harden into less dynamic structures. However, how these properties emerge from the collective interactions of many amino acids remains largely unknown. Here, we use extensive mutagenesis to identify a sequence-encoded molecular grammar underlying the driving forces of phase separation of proteins in the FUS family and test aspects of this grammar in cells. Phase separation is primarily governed by multivalent interactions among tyrosine residues from prion-like domains and arginine residues from RNA-binding domains, which are modulated by negatively charged residues. Glycine residues enhance the fluidity, whereas glutamine and serine residues promote hardening. We develop a model to show that the measured saturation concentrations of phase separation are inversely proportional to the product of the numbers of arginine and tyrosine residues. These results suggest it is possible to predict phase-separation properties based on amino acid sequences.