Cell-free formation of RNA granules: Low complexity sequence domains form dynamic fibers within hydrogels

Masato Kato, Tina W. Han, Shanhai Xie, Kevin Shi, Xinlin Du, Leeju C. Wu, Hamid Mirzaei, Elizabeth J. Goldsmith, Jamie Longgood, Jimin Pei, Nick V. Grishin, Douglas E. Frantz, Jay W. Schneider, She Chen, Lin Li, Michael R. Sawaya, David Eisenberg, Robert Tycko, Steven L. McKnight

Research output: Contribution to journalArticle

872 Scopus citations

Abstract

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. PaperClip:

Original languageEnglish (US)
Pages (from-to)753-767
Number of pages15
JournalCell
Volume149
Issue number4
DOIs
StatePublished - May 11 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    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. (2012). Cell-free formation of RNA granules: Low complexity sequence domains form dynamic fibers within hydrogels. Cell, 149(4), 753-767. https://doi.org/10.1016/j.cell.2012.04.017