Stress-Induced Low Complexity RNA Activates Physiological Amyloidogenesis

Miling Wang, Xianzun Tao, Mathieu D. Jacob, Clayton A. Bennett, J. J.David Ho, Mark L Gonzalgo, Timothy E. Audas, Stephen Lee

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Amyloid bodies (A-bodies) are inducible membrane-less nuclear compartments composed of heterogeneous proteins that adopt an amyloid-like state. A-bodies are seeded by noncoding RNA derived from stimuli-specific loci of the rDNA intergenic spacer (rIGSRNA). This raises the question of how rIGSRNA recruits a large population of diverse proteins to confer A-body identity. Here, we show that long low-complexity dinucleotide repeats operate as the architectural determinants of rIGSRNA. On stimulus, clusters of rIGSRNA with simple cytosine/uracil (CU) or adenosine/guanine (AG) repeats spanning hundreds of nucleotides accumulate in the nucleolar area. The low-complexity sequences facilitate charge-based interactions with short cationic peptides to produce multiple nucleolar liquid-like foci. Local concentration of proteins with fibrillation propensity in these nucleolar foci induces the formation of an amyloidogenic liquid phase that seeds A-bodies. These results demonstrate the physiological importance of low-complexity RNA and repetitive regions of the genome often dismissed as “junk” DNA. Wang et al. report the identification of stress-induced low-complexity ribosomal intergenic RNA that drive the formation of an amyloidogenic liquid-like phase. Concentration of proteins with fibrillation propensity by low-complexity RNA initiates an amyloidogenic program that confers A-body identity.

Original languageEnglish (US)
Pages (from-to)1713-1721.e4
JournalCell Reports
Volume24
Issue number7
DOIs
StatePublished - Aug 14 2018

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Keywords

  • amyloidogenesis
  • architectural RNA
  • beta-amyloid
  • complex coacervation
  • junk DNA
  • liquid-to-solid phase transition
  • lncRNA
  • nucleolus
  • phase separation
  • rDNA intergenic spacer

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wang, M., Tao, X., Jacob, M. D., Bennett, C. A., Ho, J. J. D., Gonzalgo, M. L., Audas, T. E., & Lee, S. (2018). Stress-Induced Low Complexity RNA Activates Physiological Amyloidogenesis. Cell Reports, 24(7), 1713-1721.e4. https://doi.org/10.1016/j.celrep.2018.07.040