Moreover, limiting the extracellular supply or blocking the synthesis of single amino acids is known to suppress global translation initiation via activation of GCN2 and phosphorylation of the translation initiation factor EIF2α (Sood et al., 2000).
We found that deletion of eIF4G1, but not eIF4G2, impairs growth and global translation initiation rates in budding yeast under standard laboratory conditions.
During exponential growth in rich media, deletion of TIF4631 reduces proliferation and global translation initiation rates, and decreases the fraction of messages engaged in translation from genes that encode small proteins from transcripts with long 3' poly(A) tails.
Furthermore, some family members regulate translation of specific mRNAs rather than participate in global translation initiation.
Recent studies have shown that eIF3f might not be necessary for global translation initiation, but rather inhibits translation.
Other eIF4E family members interact with specific mRNAs or proteins to regulate translation of those mRNAs rather than participate in global translation initiation [ 38- 41].
This is similar to S. cerevisiae, where treatment with DTT did not result in substantial reductions in global translation initiation efficiency [ 27].
A key mechanism by which global translation initiation is controlled in eukaryotes is via the activation of eIF2α kinases (Dever, 2002; Dever et al., 1992; Hinnebusch, 2005).
Its phosphorylation at Ser-51 reduces the global translation initiation while enhancing the translation of selected mRNAs, such as those activating transcription factor (Atf4), a master gene of the integrated stress response.
Like PKR (double-stranded RNA-activated protein kinase, also known as eIF2αk2), one of the eukaryotic translation inhibition factor 2α (eIF2α) kinases, PERK (eIF2ak3) also phosphorylates eIF2α at Ser 51, and phosphorylated eIF2α impedes global translation initiation to decrease the protein load in the ER [ 5].
