Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells

Abstract

Cells exposed to starvation have to adjust their metabolism to conserve energy and protect themselves. Protein synthesis is one of the major energy-consuming processes and as such has to be tightly controlled. Many mechanistic details about how starved cells regulate the process of protein synthesis are still unknown. Here, we report that the essential translation initiation factor eIF2B forms filaments in starved budding yeast cells. We demonstrate that filamentation is triggered by starvation-induced acidification of the cytosol, which is caused by an influx of protons from the extracellular environment. We show that filament assembly by eIF2B is necessary for rapid and efficient downregulation of translation. Importantly, this mechanism does not require the kinase Gcn2. Furthermore, analysis of sitespecific variants suggests that eIF2B assembly results in enzymatically inactive filaments that promote stress survival and fast recovery of cells from starvation. We propose that translation regulation through filament assembly is an efficient mechanism that allows yeast cells to adapt to fluctuating environments.

Cryo-ET detects bundled triple helices but not ladders in meiotic budding yeast

“…cerevisiae cells that were incubated in rich media [ 26 , 28 , 31 ]. Recent studies showed that when yeast cells are stressed by glucose deprivation, components of the translation machinery form large cytoplasmic filaments [ 32 , 33 ]. SM contains the less-preferred acetate as the carbon source, which may induce stress-related structures that we had not seen before.…”

Structures, functions, and mechanisms of filament forming enzymes: a renaissance of enzyme filamentation

“…Therefore, selfassembly formation by eIF2/eIF2B prevents it from doing its job, no doubt, which is initiation of translation. Confirming this, Nuske, et al (2018) 300 found that starvation induced acidification of the cytosol causes self-assembly of eIF2B (Gcn3/eIF2B-α) and downregulation of translation that is independent of the kinase Gcn2.…”

Molecular Crowding Facilitates Bundling of IMPDH Polymers and Cytoophidium Formation

“…In consistency with this model, the formation of CTPS cytoophidium was found to significantly attenuate the ubiquitination of CTPS (Sun and Liu, 2019a). In addition, the bundling of the translation initiation factor eIF2B filaments can downregulate general protein translation (Nuske et al, 2020). These could be led by reduced interactions between cytoophidium components and RNAs or proteins.…”