Regulation of translation initiation by FRAP/mTOR

Regulation of protein synthesis in eukaryotes plays a critical role in development, differentiation, cell cycle progression, cell growth, and apoptosis. Translational control allows for a more rapid response than transcriptional modulation because no mRNA synthesis, processing, or transport is required, and can be used to coordinate gene expression in systems that lack transcriptional regulation, such as reticulocytes or platelets. Translational control plays a particularly important role in early developmental processes, when localized translation is utilized to establish polarity (Wickens et al. 2000), and localized translation in neurons may be critical for learning and memory (e.g., Casadio et al. 1999). Following transcription, processing, and nucleocytoplasmic export, mRNAs are competent for translation. However, two transcripts present in identical quantities may be translated at very different rates. This phenomenon is caused, in part, by the fact that the ribosome does not bind to mRNA directly, but must be recruited to mRNA by the concerted action of a large number of eukaryotic translation initiation factors (eIFs). This recruitment step, also referred to as the initiation phase, is a complex process that culminates in the positioning of a charged ribosome (that is, an 80S ribosome loaded with an initiator tRNA in its P site) at an initiation codon. As discussed further below, the recruitment process is rate-limiting for translation in many cases, and is subject to exquisite regulation. The structure m super(7)GpppN (or the cap, where m is a methyl group and N any nucleotide) is present at the 5' end of all nuclear transcribed mRNAs, and plays an important role in the initiation process.