Projects per year
Abstract
A mutant form of the ataxin-1 protein with an expanded polyglutamine (polyQ) tract is the underlying cause of the inherited neurodegenerative disease spinocerebellar ataxia 1 (SCA1). In probing the biophysical features of the nuclear bodies (NBs) formed by polyQ-ataxin-1, we defined ataxin-1 NBs as spherical liquid protein/RNA droplets capable of rapid fusion. We observed dynamic exchange of the ataxin-1 protein into these NBs; notably, cell exposure to a pro-oxidant stress could trigger a transition to slower ataxin-1 exchange, typical of a hydrogel state, which no longer showed the same dependence on RNA or sensitivity to 1,6-hexanediol. Furthermore, we could alter ataxin-1 exchange dynamics either through modulating intracellular ATP levels, RNA helicase inhibition, or siRNA-mediated depletion of select RNA helicases. Collectively, these findings reveal the tunable dynamics of the liquid RNA/protein droplets formed by polyQ-ataxin-1.
Original language | English |
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Article number | 1557 |
Number of pages | 18 |
Journal | Scientific Reports |
Volume | 10 |
Issue number | 1 |
DOIs | |
Publication status | Published - 31 Jan 2020 |
Keywords
- imaging
- nuclear organization
Projects
- 1 Finished
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NHMRC Research Fellowship
Jans, D.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/05 → 31/12/20
Project: Research