Nejvíce citovaný článek - PubMed ID 30715564
An aggregation-prone mutant of eIF3a forms reversible assemblies escaping spatial control in exponentially growing yeast cells
Stress granules (SGs) are membrane-less assemblies arising upon various stresses in eukaryotic cells. They sequester mRNAs and proteins from stressful conditions and modulate gene expression to enable cells to resume translation and growth after stress relief. SGs containing the translation initiation factor eIF3a/Rpg1 arise in yeast cells upon robust heat shock (HS) at 46 °C only. We demonstrate that the destabilization of Rpg1 within the PCI domain in the Rpg1-3 variant leads to SGs assembly already at moderate HS at 42 °C. These are bona fide SGs arising upon translation arrest containing mRNAs, which are components of the translation machinery, and associating with P-bodies. HS SGs associate with endoplasmatic reticulum and mitochondria and their contact sites ERMES. Although Rpg1-3-labeled SGs arise at a lower temperature, their disassembly is delayed after HS at 46 °C. Remarkably, the delayed disassembly of HS SGs after the robust HS is reversed by TDP-43, which is a human protein connected with amyotrophic lateral sclerosis. TDP-43 colocalizes with HS SGs in yeast cells and facilitates cell regrowth after the stress relief. Based on our results, we propose yeast HS SGs labeled by Rpg1 and its variants as a novel model system to study functions of TDP-43 in stress granules disassembly.
- Klíčová slova
- ER, ERMES, Hsp104, Rpg1, TDP-43, eIF3, heat shock, mitochondria, stress granules, yeast,
- MeSH
- cytoplazmatická granula fyziologie MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- endoplazmatické retikulum metabolismus MeSH
- eukaryotický iniciační faktor 3 chemie genetika metabolismus MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- mitochondrie metabolismus MeSH
- reakce na tepelný šok * MeSH
- Saccharomyces cerevisiae - proteiny genetika metabolismus MeSH
- Saccharomyces cerevisiae genetika růst a vývoj metabolismus MeSH
- stabilita proteinů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- EIF3A protein, human MeSH Prohlížeč
- eukaryotický iniciační faktor 3 MeSH
- messenger RNA MeSH
- RPG1 protein, S cerevisiae MeSH Prohlížeč
- Saccharomyces cerevisiae - proteiny MeSH
- TARDBP protein, human MeSH Prohlížeč