Poster Presentation The 44th Lorne Conference on Protein Structure and Function 2019

Nuclear bodies formed by polyQ-ataxin-1 protein are liquid RNA/protein droplets with tunable dynamics (#228)

Sunyuan Zhang 1 , Elizabeth Hinde 2 , David A. Jans 3 , Marie A. Bogoyevitch 1
  1. Biochemistry and molecular biology, University of Melbourne , Parkville, Victoria 3010, Australia
  2. Bio21 Institute, University of Melbourne , Parkville, Victoria 3010, Australia
  3. Biochemistry and molecular biology, Monash University, Clayton, Victoria 3800, Australia

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. Furthermore, we could alter ataxin-1 exchange dynamics either through modulating intracellular ATP levels, 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.