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Cell-free Formation of RNA Granules: Low Complexity Sequence Domains Form Dynamic Fibers within Hydrogels
Open accessAbstract
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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