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 language | English (US) |
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Pages (from-to) | 1713-1721.e4 |
Journal | Cell Reports |
Volume | 24 |
Issue number | 7 |
DOIs | |
State | Published - Aug 14 2018 |
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)