The regulation of protein synthesis in eukaryotes is crucial for various cellular processes, including development, differentiation, cell cycle progression, and apoptosis. Translational control allows for rapid responses without the need for mRNA synthesis, processing, or transport, making it particularly important in early developmental processes and in neurons for learning and memory. The recruitment of ribosomes to mRNA is a complex process involving multiple initiation factors (eIFs), with the cap structure (m7GpppN) playing a key role in this process. The eIF4F complex, composed of eIF4E, eIF4G, and eIF4A, is essential for ribosome recruitment and mRNA scanning. The activity of these factors is regulated by phosphorylation, with eIF4E being a central regulator. Phosphorylation of eIF4E by the eIF4E binding proteins (4E-BPs) is influenced by intracellular signaling pathways, such as PI3K and FRAP/mTOR, which also regulate other translation initiation factors like S6K1 and eIF4GI. FRAP/mTOR, a mammalian homolog of the yeast Tor proteins, is a protein kinase that autophosphorylates and phosphorylates several downstream targets, including 4E-BP1 and eIF4GI. FRAP/mTOR signaling is involved in nutrient sensing and modulates translation rates of specific mRNA subpopulations, particularly those with structured 5'UTRs or containing the 5'TOP element. Rapamycin, a macrocyclic antibiotic, inhibits FRAP/mTOR activity and blocks translation initiation, leading to a precipitous translational arrest in yeast and mammalian cells. The effects of rapamycin on translation are mediated through the modulation of 4E-BP1 and eIF4GI phosphorylation, as well as other translation initiation factors.The regulation of protein synthesis in eukaryotes is crucial for various cellular processes, including development, differentiation, cell cycle progression, and apoptosis. Translational control allows for rapid responses without the need for mRNA synthesis, processing, or transport, making it particularly important in early developmental processes and in neurons for learning and memory. The recruitment of ribosomes to mRNA is a complex process involving multiple initiation factors (eIFs), with the cap structure (m7GpppN) playing a key role in this process. The eIF4F complex, composed of eIF4E, eIF4G, and eIF4A, is essential for ribosome recruitment and mRNA scanning. The activity of these factors is regulated by phosphorylation, with eIF4E being a central regulator. Phosphorylation of eIF4E by the eIF4E binding proteins (4E-BPs) is influenced by intracellular signaling pathways, such as PI3K and FRAP/mTOR, which also regulate other translation initiation factors like S6K1 and eIF4GI. FRAP/mTOR, a mammalian homolog of the yeast Tor proteins, is a protein kinase that autophosphorylates and phosphorylates several downstream targets, including 4E-BP1 and eIF4GI. FRAP/mTOR signaling is involved in nutrient sensing and modulates translation rates of specific mRNA subpopulations, particularly those with structured 5'UTRs or containing the 5'TOP element. Rapamycin, a macrocyclic antibiotic, inhibits FRAP/mTOR activity and blocks translation initiation, leading to a precipitous translational arrest in yeast and mammalian cells. The effects of rapamycin on translation are mediated through the modulation of 4E-BP1 and eIF4GI phosphorylation, as well as other translation initiation factors.