RNA buffers the phase separation behavior of prion-like RNA binding proteins.

Maharana, Shovamayee; Wang, Jie; Papadopoulos, Dimitrios; Richter, Doris; Pozniakovsky, Andrei I.; Poser, Ina; Bickle, Marc; Rizk, Sandra; Guillén-Boixet, Jordina; Franzmann, Titus; Jahnel, Marcus; Marrone, Lara; Chang, Young-Tae; Sterneckert, Jared; Tomancak, Pavel; Hyman, Anthony; Alberti, Simon

doi:10.1126/science.aar7366

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RNA buffers the phase separation behavior of prion-like RNA binding proteins.

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

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

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Papadopoulos, Dimitrios
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Richter, Doris
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/persons219545

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

/persons/resource/persons219009

Bickle, Marc
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons231686

Guillén-Boixet, Jordina
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

/persons/resource/persons219166

Franzmann, Titus
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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

/persons/resource/persons219742

Tomancak, Pavel
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;

/persons/resource/persons218962

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

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Citation

Maharana, S., Wang, J., Papadopoulos, D., Richter, D., Pozniakovsky, A. I., Poser, I., et al. (2018). RNA buffers the phase separation behavior of prion-like RNA binding proteins. Science (New York, N.Y.), 360(6391), 918-921. doi:10.1126/science.aar7366.

Cite as: https://hdl.handle.net/21.11116/0000-0004-5B96-D

Abstract

Prion-like RNA binding proteins (RBPs) such as TDP43 and FUS are largely soluble in the nucleus but form solid pathological aggregates when mislocalized to the cytoplasm. What keeps these proteins soluble in the nucleus and promotes aggregation in the cytoplasm is still unknown. We report here that RNA critically regulates the phase behavior of prion-like RBPs. Low RNA/protein ratios promote phase separation into liquid droplets, whereas high ratios prevent droplet formation in vitro. Reduction of nuclear RNA levels or genetic ablation of RNA binding causes excessive phase separation and the formation of cytotoxic solid-like assemblies in cells. We propose that the nucleus is a buffered system in which high RNA concentrations keep RBPs soluble. Changes in RNA levels or RNA binding abilities of RBPs cause aberrant phase transitions.