TIA1 potentiates tau phase separation and promotes generation of toxic oligomeric tau.

ABSTRACT: Tau protein plays an important role in the biology of stress granules and in the stress response of neurons, but the nature of these biochemical interactions is not known. Here we show that the interaction of tau with RNA and the RNA binding protein TIA1 is sufficient to drive phase separation of tau at physiological concentrations, without the requirement for artificial crowding agents such as polyethylene glycol (PEG). We further show that phase separation of tau in the presence of RNA and TIA1 generates abundant tau oligomers. Prior studies indicate that recombinant tau readily forms oligomers and fibrils in vitro in the presence of polyanionic agents, including RNA, but the resulting tau aggregates are not particularly toxic. We discover that tau oligomers generated during copartitioni

SUBMITTER: Ash PEA 

PROVIDER: S-EPMC7936275 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature