Translational controls impinging on the 5'-untranslated region and initiation factor proteins

Translation of eukaryotic mRNAs is generally initiated by the scanning ribosome mechanism. This can be downregulated by high affinity protein binding to cap-proximal RNA motifs. Translation can also be regulated by short open reading frames within the 5'-untranslated region. A key factor for initiation is eIF4F, in which one of the polypeptide chains, eIF4G, seems to have a bridging function and binds three other factors at separate sites: eIF4E (the cap-binding factor), the helicase eIF4A, and eIF3, which also interacts with 40S ribosomal subunits. Initiation is regulated by the MAP kinase and rapamycin-sensitive signalling pathways, which control phosphorylation of eIF4E and 4E-BP1, a protein which in the dephosphorylated form binds and sequesters eIF4E.