Regulation of TIA-1 Condensates: Zn2+ and RGG Motifs Promote Nucleic Acid Driven LLPS and Inhibit Irreversible Aggregation

• DOI: 10.3389/fmolb.2022.960806
• Publication Date: 2022-07-14T04:47:55Z
• Authors: Danella L. West; Fionna E. Loughlin; Francisco Rivero-...; Naveen Vankadari; Alejandro Velázqu...; Laura Corrales-Gu...; Irene Díaz-Moreno; Jacqueline A. Wilce
• Keywords: Stress granule; Granule (geology)

Stress granules are non-membrane bound RNA-protein essential for survival during acute cellular stress. TIA-1 is a key protein in the formation of stress that undergoes liquid-liquid phase separation by association with specific RNAs and protein-protein interactions. However, fundamental properties enable phase-separation also render susceptible to irreversible fibrillar aggregates. Despite this, within physiological granules, not present as fibrils, pointing additional factors cell prevent aggregation. Here we show heterotypic interactions granule co-factors Zn2+ RGG-rich regions from FUS each act together nucleic acid induce TIA-1. In contrast, these do enhance induced fibril TIA-1, but rather robustly inhibit process. NMR titration experiments revealed between H94 H96 RRM2 Strikingly, this interaction promotes multimerization independently prion-like domain. Thus, through different molecular mechanisms, promote suppress aggregates, potentially contributing dynamic nature protection they provide.