The physiological and pathological biophysics of phase separation and gelation of RNA binding proteins in amyotrophic lateral sclerosis and fronto-temporal lobar degeneration.
Phillips, Emma C
Randle, Suzanne J
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St George-Hyslop, P., Lin, Q., Miyashita, A., Phillips, E. C., Qamar, S., Randle, S. J., & Wang, G. (2018). The physiological and pathological biophysics of phase separation and gelation of RNA binding proteins in amyotrophic lateral sclerosis and fronto-temporal lobar degeneration.. Brain research, 1693 (Pt A), 11-23. https://doi.org/10.1016/j.brainres.2018.04.036
Many RNA binding proteins, including FUS, contain moderately repetitive, low complexity, intrinsically disordered domains. These sequence motifs have recently been found to underpin reversible liquid: liquid phase separation and gelation of these proteins, permitting them to reversibly transition from a monodispersed state to liquid droplet- or hydrogel-like states. This function allows the proteins to serve as scaffolds for the formation of reversible membraneless intracellular organelles such as nucleoli, stress granules and neuronal transport granules. Using FUS as an example, this review examines the biophysics of this physiological process, and reports on how mutations and changes in post-translational state alter phase behaviour, and lead to neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
Temporal Lobe, Cytoplasmic Granules, Humans, Amyotrophic Lateral Sclerosis, Neurodegenerative Diseases, RNA-Binding Proteins, RNA-Binding Protein FUS, DNA-Binding Proteins, Biophysics, Protein Processing, Post-Translational, Mutation, Frontotemporal Lobar Degeneration, Frontotemporal Dementia, Protein Domains
Wellcome Trust (203249/Z/16/Z)
External DOI: https://doi.org/10.1016/j.brainres.2018.04.036
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279263
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/