TIA-1 Self-Multimerization, Phase Separation, and Recruitment into Stress Granules Are Dynamically Regulated by Zn2+

TIA-1 Self-Multimerization, Phase Separation, and Recruitment into Stress Granules Are Dynamically Regulated by Zn2+

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Summary: Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and Mens Shavers modulate cell signaling by sequestering key signal transduction proteins.These and other functions of stress granules facilitate an adaptive cellular response to environmental adversity.A key component of stress granules is the prion-related RNA-binding protein, T cell intracellular antigen-1 (TIA-1).Here, we report that recombinant TIA-1 undergoes rapid multimerization and phase separation in the presence of divalent zinc, which can be reversed by the zinc chelator, TPEN.

Similarly, the formation and maintenance of TIA-1-positive stress granules in arsenite-treated cells are inhibited by TPEN.In addition, Zn2+ is released in cells treated with arsenite, before stress granule formation.These findings suggest that Toy Box Zn2+ is a physiological ligand of TIA-1, acting as a stress-inducible second messenger to promote multimerization of TIA-1 and subsequent localization into stress granules.: Rayman et al.

show that Zn2+ is a stress-inducible second messenger that triggers self-multimerization and phase separation of TIA-1 and regulates dynamic recruitment of TIA-1 into stress granules.This mechanism is part of an adaptive cellular response to environmental adversity.Keywords: TIA-1, TIA1, stress granules, cellular stress, functional prion, phase separation, zinc regulation.