PROTEIN AGGREGATION

Buffering transition

Science https://doi.org/10.1126/science.aar7366 (2018)

Aberrant aggregation of normally soluble proteins into insoluble amyloid is involved in the onset and the progression of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In the neurons of ALS patients, aggregation of prion-like RNA-binding proteins (RBPs) usually occurs in the cytoplasm rather than the nucleus. To investigate what prevents prion-like RBPs from forming solid-like aggregates in the nucleus, Maharana et al. used in vitro phase-separation assays and fluorescence correlation spectroscopy to show that RNA blocks the liquid–solid phase transition of prion-like RBPs, which is a prerequisite of aggregation. In living cells, assemblies of prion-like RBPs are observed by reducing the concentration of nuclear RNAs, by increasing intranuclear protein expression, or by impairing the RNA-binding ability of proteins. Photobleaching experiments showed that RNA kept condensates formed by prion-like RBPs in a dynamic state and prevented the formation of solid pathological assemblies. Overall, the findings suggest that nuclear RNA buffers the phase separation behavior of prion-like RBPs, provide insight into the chemical characteristics of this type of protein, and deepen the understanding of the pathological cause of prion-like RBP-related neurodegenerative diseases.

Credit: AAAS

Author information

Affiliations

Authors

Corresponding author

Correspondence to Yiyun Song.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Song, Y. Buffering transition. Nat Chem Biol 14, 525 (2018). https://doi.org/10.1038/s41589-018-0076-6

Download citation

Search

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing