Journal article

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

Sunyuan Zhang, Elizabeth Hinde, Molly Parkyn Schneider, David A Jans, Marie A Bogoyevitch

Scientific Reports | NATURE PUBLISHING GROUP | Published : 2020

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 dynami..

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University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council (NHMRC)


Funding Acknowledgements

This work was supported by National Health and Medical Research Council (NHMRC) Project Grant APP1121907. S. Z. is a recipient of the Melbourne International Research Scholarship at the University of Melbourne, EH is an NHMRC Career Development Fellow (APP1124762) and D.A.J. is an NHMRC Senior Principal Research Fellow (APP1103050). The GFP-ataxin-1[85Q] and GFP-ataxin-1[30Q] plasmids were provided by D Hatters (University of Melbourne) and the GFP-ataxin-1[85Q] mutant plasmids (GFP-ataxin1.SAD and GFP-ataxin-1S776A) were provided by W.-K. Chen (University of Melbourne). We acknowledge access to the Biological Optical Microscopy Platform at the University of Melbourne.