dc.creator | West, Danella L. | es |
dc.creator | Loughlin, Fionna E. | es |
dc.creator | Rivero Rodríguez, Francisco | es |
dc.creator | Vankadari, Naveen | es |
dc.creator | Velázquez Cruz, Alejandro | es |
dc.creator | Corrales Guerrero, Laura | es |
dc.creator | Díaz Moreno, Irene | es |
dc.creator | Wilce, Jacqueline A. | es |
dc.date.accessioned | 2022-08-30T15:31:58Z | |
dc.date.available | 2022-08-30T15:31:58Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | West, D.L., Loughlin, F.E., Rivero Rodríguez, F., Vankadari, N., Velázquez Cruz, A., Corrales Guerrero, L.,...,Wilce, J.A. (2022). Regulation of TIA-1 Condensates: Zn2+ and RGG Motifs Promote Nucleic Acid Driven LLPS and Inhibit Irreversible Aggregation. Frontiers in Molecular Biosciences, 9, 960806. | |
dc.identifier.issn | 2296-889X | es |
dc.identifier.uri | https://hdl.handle.net/11441/136543 | |
dc.description.abstract | Stress granules are non-membrane bound RNA-protein granules essential for survival during acute cellular stress. TIA-1 is a key protein in the formation of stress granules that undergoes liquid-liquid phase separation by association with specific RNAs and protein-protein interactions. However, the fundamental properties of the TIA-1 protein that enable phase-separation also render TIA-1 susceptible to the formation of irreversible fibrillar aggregates. Despite this, within physiological stress granules, TIA-1 is not present as fibrils, pointing to additional factors within the cell that prevent TIA-1 aggregation. Here we show that heterotypic interactions with stress granule co-factors Zn2+ and RGG-rich regions from FUS each act together with nucleic acid to induce the liquid-liquid phase separation of TIA-1. In contrast, these co-factors do not enhance nucleic acid induced fibril formation of TIA-1, but rather robustly inhibit the process. NMR titration experiments revealed specific interactions between Zn2+ and H94 and H96 in RRM2 of TIA-1. Strikingly, this interaction promotes multimerization of TIA-1 independently of the prion-like domain. Thus, through different molecular mechanisms, these stress granule co-factors promote TIA-1 liquid-liquid phase separation and suppress fibrillar aggregates, potentially contributing to the dynamic nature of stress granules and the cellular protection that they provide. | es |
dc.description.sponsorship | National Health and Medical Research Council of Australia APP1105801 | es |
dc.description.sponsorship | Australian Research Council DP200102737 | es |
dc.description.sponsorship | Junta de Andalucía BIO198, US-1254317, P18- FR-3487, P18-HO-4091 | es |
dc.description.sponsorship | Ministerio de Ciencia e Innovación PGC 2018-096049- BI00, PID2021-126663NB-I00 | es |
dc.format | application/pdf | es |
dc.format.extent | 14 p. | es |
dc.language.iso | eng | es |
dc.publisher | Frontiers Media S.A. | es |
dc.relation.ispartof | Frontiers in Molecular Biosciences, 9, 960806. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Amyloid fibril | es |
dc.subject | Liquid-liquid phase separation | es |
dc.subject | Prion-like domain | es |
dc.subject | RGG motif | es |
dc.subject | RNA binding protein | es |
dc.subject | RRM | es |
dc.subject | TIA1 | es |
dc.subject | Zinc | es |
dc.title | Regulation of TIA-1 Condensates: Zn2+ and RGG Motifs Promote Nucleic Acid Driven LLPS and Inhibit Irreversible Aggregation | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular | es |
dc.relation.projectID | APP1105801 | es |
dc.relation.projectID | DP200102737 | es |
dc.relation.projectID | BIO198 | es |
dc.relation.projectID | US-1254317 | es |
dc.relation.projectID | P18- FR-3487 | es |
dc.relation.projectID | P18-HO-4091 | es |
dc.relation.projectID | PGC 2018-096049- BI00 | es |
dc.relation.projectID | PID2021-126663NB-I00 | es |
dc.relation.publisherversion | https://doi.org/10.3389/fmolb.2022.960806 | es |
dc.identifier.doi | 10.3389/fmolb.2022.960806 | es |
dc.journaltitle | Frontiers in Molecular Biosciences | es |
dc.publication.volumen | 9 | es |
dc.publication.initialPage | 960806 | es |
dc.contributor.funder | National Health and Medical Research Council. Australia | es |
dc.contributor.funder | Australian Research Council | es |
dc.contributor.funder | Junta de Andalucía | es |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |