Reference no: EM133822461

Question

The formation of stress granules when translation initiation is inhibited suggests that these granules contain mRNAs stalled in the process of translation initiation, which is consistent with their composition. Stress granules typically contain poly(A)+ mRNA, 40S ribosomal subunits, eIF4E, eIF4G, eIF4A, eIF4B, poly(A)-binding protein (Pabp), eIF3, and eIF2 (Kedersha et al., 1999, Kedersha et al., 2002, Kimball et al., 2003, Mazroui et al., 2006, Anderson and Kedersha, 2006), although the composition can vary. For example, in Saccharomyces cerevisiae, heat shock-induced stress granules contain eIF3, whereas glucose deprivation-induced stress granules do not (Grousl et al., 2009, Hoyle et al., 2007, Buchan et al., 2008). Depending on experimental conditions, stress granules can also harbor many other protein components including RNA helicases, translation and stability regulators, and factors involved in cell signaling (see Table S1 available online). An unresolved issue is the nature of the mRNP complex within stress granules. One possibility is that the mRNAs, translation initiation factors, and 40S ribosomal subunits within stress granules are assembled into a 48S preinitiation complex. However, many stress responses inhibit translation upstream of 48S complex formation by impairing eIF4E function or via phosphorylation of eIF2, which then limits the formation of a 43S complex containing eIF2, the initiator tRNA, eIF3, and the 40S subunit (Sonenberg and Hinnebusch, 2009).