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Cell-free Formation of RNA Granules: Low Complexity Sequence Domains Form Dynamic Fibers within Hydrogels
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Eukaryotic cells contain assemblies of RNAs and proteins termed RNA granules. Many proteins within these bodies contain KH or RRM RNA-binding domains as well as low complexity (LC) sequences of unknown function. We discovered that exposure of cell or tissue lysates to a biotinylated isoxazole (b-isox) chemical precipitated hundreds of RNA-binding proteins with significant overlap to the constituents of RNA granules. The LC sequences within these proteins are both necessary and sufficient for b-isox-mediated aggregation, and these domains can undergo a concentration-dependent phase transition to a hydrogel-like state in the absence of the chemical. X-ray diffraction and EM studies revealed the hydrogels to be composed of uniformly polymerized amyloid-like fibers. Unlike pathogenic fibers, the LC sequence-based polymers described here are dynamic and accommodate heterotypic polymerization. These observations offer a framework for understanding the function of LC sequences as well as an organizing principle for cellular structures that are not membrane bound.
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“This module contained proteins often found in RNA granules [48]”
From Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease (2018) · cites this paper as [48]
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Metadata
- Authors
- Kato, M., Han, T. W., Xie, S., Shi, K., Du, X., Wu, L. C., Mirzaei, H., Goldsmith, E. J., Longgood, J., Pei, J., Grishin, N. V., Frantz, D. E., Schneider, J. W., Chen, S., Li, L., Sawaya, M. R., Eisenberg, D., Tycko, R., & McKnight, S. L.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- National Institute of Biological Sciences, Beijing (CN)
- National Institutes of Health (US)
- Corresponding author
- McKnight, Steven L.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 149
- Issue
- 4
- Pages
- 753-767
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6347373
- OpenAlex
- W2120156669
- Cited by
- 2,012
- References
- 51
- Citations by year
- 2026: 100 · 2025: 104 · 2024: 130 · 2023: 139 · 2022: 195 · 2021: 227 · 2020: 198 · 2019: 167 · 2018: 177 · 2017: 128 · 2016: 127 · 2015: 120 · 2014: 91 · 2013: 83 · 2012: 22
- FWCI
- 40.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (ZIADK075031)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- RNA granules, low-complexity sequences, RNA-binding proteins, KH domain, RRM domain, protein aggregation, hydrogels, phase separation, cell-free system, protein condensates
- MeSH terms
- Animals, Brain, Cell-Free System, Cytoplasmic Granules, Male, Models, Molecular, RNA, Testis, X-Ray Diffraction, RNA-Binding Proteins, Caenorhabditis elegans, Hydrogel, Polyethylene Glycol Dimethacrylate, NIH 3T3 Cells, Mice, Embryonic Stem Cells
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