2. Academic Validation
  3. Cell-free formation of RNA granules: low complexity sequence domains form dynamic fibers within hydrogels

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

  • Cell. 2012 May 11;149(4):753-67. doi: 10.1016/j.cell.2012.04.017.
Masato Kato 1,  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
Affiliations

Affiliation

  • 1 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, 75390-9152, USA.
PMID: 22579281 DOI: 10.1016/j.cell.2012.04.017
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.

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