Stress-Induced Low Complexity RNA Activates Physiological Amyloidogenesis
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 rec...
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Veröffentlicht in: | Cell reports (Cambridge) 2018-08, Vol.24 (7), p.1713-1721.e4 |
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Sprache: | eng |
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Zusammenfassung: | 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.
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•Stressors induce low-complexity RNA from “junk” repeats of the rDNA intergenic spacer•Nucleolar low-complexity RNA initiates an amyloidogenic liquid phase•Self-assembly of amyloidogenic proteins drives amyloid bodies•Dinucleotide repeats are functional elements of noncoding RNA
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. |
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ISSN: | 2211-1247 2211-1247 |
DOI: | 10.1016/j.celrep.2018.07.040 |