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

被引：762

作者：

Maharana, Shovamayee ^{[1
]}

Wang, Jie ^{[1
]}

Papadopoulos, Dimitrios K. ^{[1
,2
]}

Richter, Doris ^{[1
]}

Pozniakovsky, Andrey ^{[1
]}

Poser, Ina ^{[1
]}

Bickle, Marc ^{[1
]}

Rizk, Sandra ^{[1
,3
]}

Guillen-Boixet, Jordina ^{[1
]}

Franzmann, Titus M. ^{[1
]}

Jahnel, Marcus ^{[1
,4
]}

Marrone, Lara ^{[5
]}

Chang, Young-Tae ^{[6
,7
]}

Sterneckert, Jared ^{[5
]}

Tomancak, Pavel ^{[1
]}

Hyman, Anthony A. ^{[1
]}

Alberti, Simon ^{[1
]}

机构：

[1] Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany

[2] Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Crewe Rd, Edinburgh EH4 2XU, Midlothian, Scotland

[3] Tech Univ Dresden, Cube Ctr Mol Bioengn B, Arnoldstr 18, D-01307 Dresden, Germany

[4] Tech Univ Dresden, Ctr Biotechnol, Tatzberg 47-49, D-01307 Dresden, Germany

[5] Tech Univ Dresden, CMCB, DFG Ctr Regenerat Therapies Dresden, D-01307 Dresden, Germany

[6] Inst for Basic Sci Korea, Ctr Self Assembly & Complex, Pohang 37673, South Korea

[7] Pohang Univ Sci & Technol POSTECH, Dept Chem, Pohang 37673, South Korea

来源：

SCIENCE | 2018年 / 360卷 / 6391期

基金：

欧洲研究理事会;

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; FUS MUTATIONS; TOXIC GAIN; TDP-43; ALS; TRANSITION; DEGENERATION; MECHANISM; DOMAINS; DISEASE;

D O I：

10.1126/science.aar7366

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 RNAcritically 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.

引用

页码：918 / 921

页数：4

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