11/1/2022 0 Comments Initiater ugly produce![]() ![]() In mammalian cells, the assembly of SGs is initiated by the phosphorylation of eIF2α ( Kedersha et al., 1999), a translation initiation factor that loads the initiator tRNA onto the small ribosomal subunit (reviewed by Berlanga et al., 1998 Gray and Wickens, 1998). Stress granules (SGs) are discrete cytoplasmic foci at which untranslated mRNAs accumulate in cells subjected to environmental stress ( Nover et al., 1983, 1989 Scharf et al., 1998 Kedersha et al., 1999, 2000). ![]() We discuss these results in the context of a translational checkpoint model wherein TIA and eIF2 are functional antagonists of translational initiation, and in which lack of ternary complex drives SG assembly. Surprisingly, phospho-eIF2α is recruited to SGs that are disassembling in cells recovering from arsenite-induced stress. Cells expressing a phosphomimetic mutant (S51D) of eIF2α assemble SGs of similar composition, confirming that the recruitment of these factors is a direct consequence of blocked translational initiation and not due to other effects of arsenite. In contrast, eIF2 is not a component of newly assembled SGs. We now show that most components of the 48S preinitiation complex (i.e., small, but not large, ribosomal subunits, eIF3, eIF4E, eIF4G) are coordinately recruited to SGs in arsenite-stressed cells. SGs appear to be in equilibrium with polysomes, but the nature of this relationship is obscure. The resulting untranslated mRNA is dynamically routed to discrete cytoplasmic foci known as stress granules (SGs), a process requiring the related RNA-binding proteins TIA-1 and TIAR. ![]() Environmental stress-induced phosphorylation of eIF2α inhibits protein translation by reducing the availability of eIF2-GTP-tRNA iMet, the ternary complex that joins initiator tRNA Met to the 43S preinitiation complex. ![]()
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