Journal
CELL REPORTS
Volume 24, Issue 7, Pages 1713-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.07.040
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Funding
- National Institute of General Medical Sciences [R01GM115342]
- National Cancer Institute of the NIH [R01CA200676]
- Sylvester Comprehensive Cancer Center
- Canadian Institutes of Health Research (CIHR) [15389]
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Amyloid bodies (A-bodies) are inducible membraneless 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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