Title | RNA stores tau reversibly in complex coacervates |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Zhang X, Lin Y, Eschmann NA, Zhou H, Rauch JN, Hernandez I, Guzman E, Kosik KS, Han S |
Journal | PLOS Biology |
Volume | 15 |
Pagination | 1-28 |
Date Published | 07 |
Abstract | Author summary Tau is a common neuronal protein that, under circumstances and conditions not well understood to date, self-assembles into intracellular aggregates in several neurodegenerative diseases including Alzheimer disease. These aggregates are formed of fibrous polymers. The mechanism by which this critical transition from a soluble protein to insoluble fibrous material occurs is unknown. We have discovered a novel state in which many tau molecules become compacted into a protein-rich droplet while maintaining their solubility and native-like protein conformations. Chemists refer to this dense liquid droplet state as a complex coacervate phase, and it is held together by the opposite charges of their constituents, ions, and water. In the case of the tau protein, the oppositely charged constituent is RNA. Indeed, we found that in human neuronal cell culture, tau selectively binds to a category of RNA known as tRNA. Interestingly, tau and RNA favorably condense to a complex coacervate phase when the charges between them are matched and at elevated temperatures, such that tau-RNA droplets could be observed at physiologically viable protein concentrations simply by increasing the temperature from room to physiological temperatures. When the tau-RNA–dense droplets are incubated together over time, tau transitions to a conformation similar to that found in pathological fibers. Our experiments therefore demonstrate physicochemical properties of tau that may predispose it to undergo changes associated with neurodegenerative disease. |
URL | https://doi.org/10.1371/journal.pbio.2002183 |
DOI | 10.1371/journal.pbio.2002183 |