The McInerney Laboratory at Karolinska Institutet, Stockholm, Sweden
Stress granules (SGs) are dynamic sites of mRNA storage, which are formed in the cytoplasm of cells under many types of environmental stress. The sequestration of mRNAs into these translationally silent cytoplasmic foci contributes to the rapid redirection of translation from housekeeping proteins to heat-shock proteins and other stress response factors. In 2005, we showed that SFV infection induces the very transient appearance of SGs in the cytoplasm (McInerney et al., 2005). The timing if this corelated with the change in profile of protein production from host to viral. In infected cells, SGs are induced by the protein kinase R (PKR)-dependent phosphorylation of eukaryotic translation initiation factor 2 but the cause of SG disassembly was not clear at that time. Since publication of that paper, transient SG formation has been revealed to be a common feature of many diverse viral infections.
We have recently shown that SG disruption by SFV is mediated by the recruitment of the SG protein G3BP into viral replication complexes (Panas et al., 2012). We showed that this recruitment is dependent on two FGDF motifs in the extreme C terminal end of nsP3 (Panas et al., 2015).
Publications on this topic
Schulte T, Liu L, Panas MD, Thaa, B, Dickson N, Götte B, Achour A and McInerney GM. (2016) Combined structural, biochemical and cellular evidence demonstrates that both FGDF motifs in alphavirus nsP3 are required for efficient replication. Open Biology, doi: 10.1098/rsob.160078.
Kedersha N, Panas MD, Achorn CA, Lyons S, Tisdale S, Hickman T, Thomas M, Lieberman J, McInerney GM, Ivanov P, Anderson P. (2016) G3BP-Caprin1-USP10 complexes mediate stress granule condensation and associate with 40S subunits. J Cell Biol. 212:845-60.
McInerney, G.M. (2015) FGDF Motif Regulation of Stress Granule Formation. DNA Cell Biol. 34:557–5604.
Panas, M.D., Kedersha, N. and McInerney, G.M. (2015) Methods for the characterization of stress granules in virus infected cells. Methods. doi:10.1016/j.ymeth.2015.04.009.
Panas, M.D., Schulte, T., Thaa, B., Sandalova, T., Achour, A., Kedersha, N.L. and McInerney G.M. (2015). Viral and cellular proteins containing FGDF motifs bind G3BP to block stress granule formation. PLoS Pathogens,11(2):e1004659.
Panas, M.D., Ahola, T. and McInerney, G.M. (2014). The C-terminal repeat domains of nsP3 from the Old World alphaviruses bind directly to G3BP. J Virol, 88:5888-5893.
Panas, M.D., Varjak, M., Lulla, A., Eng, K.E., Merits, M., Karlsson Hedestam, G.B. and McInerney, G.M. (2012). Sequestration of G3BP coupled with efficient translation inhibits stress granules in Semliki Forest virus infection. Mol Biol Cell, 23:4701-4712.
McInerney, G.M., Kedersha, N.L., Kaufman, R.J., Anderson, P. and Liljeström P. (2005). Importance of eIF2alpha phosphorylation and stress granule assembly in alphavirus translation regulation. Mol Biol Cell 16:3753–3763.