Lysine/RNA-interactions drive and regulate biomolecular condensation
| Autor: | Dorothee Dormann, Maria-Sol Cima-Omori, Tina Ukmar-Godec, Saskia Hutten, Eckhard Mandelkow, Jacek Biernat, Nasrollah Rezaei-Ghaleh, Matthew P. Grieshop, Johannes Söding, Markus Zweckstetter |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Arginine Lysine General Physics and Astronomy genetics [Alzheimer Disease] RNA-binding proteins 02 engineering and technology lysine RNA chemistry [RNA] genetics [RNA] lcsh:Science Multidisciplinary Chemistry Acetylation 021001 nanoscience & nanotechnology metabolism [Lysine] metabolism [RNA] Proteome ddc:500 0210 nano-technology metabolism [Alzheimer Disease] Science tau Proteins Cytoplasmic Granules complex mixtures General Biochemistry Genetics and Molecular Biology Article Cell Line 03 medical and health sciences Stress granule Alzheimer Disease Humans genetics [Lysine] chemistry [Lysine] chemistry [tau Proteins] Colocalization General Chemistry In vitro metabolism [Cytoplasmic Granules] metabolism [tau Proteins] genetics [tau Proteins] 030104 developmental biology genetics [Cytoplasmic Granules] Biophysics bacteria lcsh:Q Solution-state NMR |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) Nature Communications 10(1), 2909 (2019). doi:10.1038/s41467-019-10792-y |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-10792-y |
| Popis: | Cells form and use biomolecular condensates to execute biochemical reactions. The molecular properties of non-membrane-bound condensates are directly connected to the amino acid content of disordered protein regions. Lysine plays an important role in cellular function, but little is known about its role in biomolecular condensation. Here we show that protein disorder is abundant in protein/RNA granules and lysine is enriched in disordered regions of proteins in P-bodies compared to the entire human disordered proteome. Lysine-rich polypeptides phase separate into lysine/RNA-coacervates that are more dynamic and differ at the molecular level from arginine/RNA-coacervates. Consistent with the ability of lysine to drive phase separation, lysine-rich variants of the Alzheimer’s disease-linked protein tau undergo coacervation with RNA in vitro and bind to stress granules in cells. Acetylation of lysine reverses liquid–liquid phase separation and reduces colocalization of tau with stress granules. Our study establishes lysine as an important regulator of cellular condensation. Processing bodies (P-bodies) are non-membrane-bound protein/RNA granules in the cytosol. Here the authors combine bioinformatics, NMR and cell based assays and find that lysine is enriched in the disordered regions of P-body-associated proteins and show that lysine-rich polypeptides form highly dynamic lysine/RNA-coacervates and lysine acetylation reverses liquid-liquid phase separation. |
| Databáze: | OpenAIRE |
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