Arabidopsis thaliana G3BP Ortholog Rescues Mammalian Stress Granule Phenotype across Kingdoms

Abstract

Stress granules (SGs) are dynamic RNA–protein complexes localized in the cytoplasm that rapidly form under stress conditions and disperse when normal conditions are restored. The formation of SGs depends on the Ras-GAP SH3 domain-binding protein (G3BP). Formations, interactions and functions of plant and human SGs are strikingly similar, suggesting a conserved mechanism. However, functional analyses of plant G3BPs are missing. Thus, members of the Arabidopsis thaliana G3BP (AtG3BP) protein family were investigated in a complementation assay in a human G3BP knock-out cell line. It was shown that two out of seven AtG3BPs were able to complement the function of their human homolog. GFP-AtG3BP fusion proteins co-localized with human SG marker proteins Caprin-1 and eIF4G1 and restored SG formation in G3BP double KO cells. Interaction between AtG3BP-1 and -7 and known human G3BP interaction partners such as Caprin-1 and USP10 was also demonstrated by co-immunoprecipitation. In addition, an RG/RGG domain exchange from Arabidopsis G3BP into the human G3BP background showed the ability for complementation. In summary, our results support a conserved mechanism of SG function over the kingdoms, which will help to further elucidate the biological function of the Arabidopsis G3BP protein family.

Nuclear Localization of G3BP6 Is Essential for the Flowering Transition in Arabidopsis

“…G3BPs are also well-known to play an important role in viral immunity, since SGs are the primary target of virus infection [12]. In the model plant Arabidopsis, seven G3BP-like proteins have been identified with both the NTF2 and RRM domains [13,14]. This also shows that all plant G3BPs, like human and animal G3BPs, promote SG formation.…”

“…Previous studies have suggested functional similarities between human and Arabidopsis G3BPs [14,15]. To gain insights into the expression patterns of G3BPs in Arabidopsis, we analyzed the RNA-seq data from the intergraded Arabidopsis RNA-seq Database (http://ipf.…”

“…This also shows that all plant G3BPs, like human and animal G3BPs, promote SG formation. A G3BP-like protein in Arabidopsis was identified as related to SG formation and played a role in virus resistance [14]. Arabidopsis G3BP orthologues can rescue mammalian SG formation, suggesting a general pathway of SG formation over living organisms [15].…”

Research Progress in RNA-Binding Proteins

“…It destabilises the messenger through the interaction with YTHDF2 that transfers it to repressive condensates, such as P-bodies and stress granules (SGs) [17]. Two research papers in this Special Issue focus on SGs, their conserved components and some new, unexpected properties [1,2]. Stress granules typically form, as the name suggests, under stress conditions, which activate eIF2α kinases that phosphorylate, and thereby inactivate, the initiation factor eIF2.…”

“…As it is often the case with plants, the A. thaliana genome encodes as many as seven G3BP homologues, raising questions of their respective molecular roles and their involvement in SG formation. An elegant study by Reuper et al in this Special Issue leverages trans-kingdom functional complementation to single out two plant G3BP-like proteins that can rescue sodium arsenite-induced SG formation in human cells that lack both native G3BP homologues [1]. Even more strikingly, domain swaps, in which the RG/RGG domains of the plant proteins were grafted on the human G3BP-1 scaffold, all turned out to be proficient in SG formation.…”