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

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• 作者：Masato Kato¹ ; Tina  ; W. Han¹ ; Shanhai Xie¹ ; Kevin Shi¹ ; Xinlin Du¹ ; Leeju  ; C. Wu¹ ; Hamid Mirzaei¹ ; Elizabeth  ; J. Goldsmith¹ ; Jamie Longgood¹ ; Jimin Pei¹ ; ³ ; Nick  ; V. Grishin¹ ; ³ ; Douglas  ; E. Frantz⁴ ; Jay  ; W. Schneider² ; She Chen⁵ ; Lin Li⁵ ; Michael  ; R. Sawaya⁶ ; David Eisenberg⁶ ; Robert Tycko⁷ ; Steven  ; L. McKnight¹ ; ^{steven.mcknight@utsouthwestern.edu}
• 刊名：Cell
• 出版年：2012
• 期刊代码：50_00928674
• 类别：med
• 出版时间：11 May, 2012
• 卷：149
• 期：4
• 页码：753-767
• 文件大小：2087 K

摘要

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Summary

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聽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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