Translational Control

Pathway Description:

The synthesis of new proteins is a highly regulated process that allows rapid cellular responses to diverse stimuli at the post-transcriptional level. Nine key eukaryotic translation initiation factors (eIFs) catalyze the assembly of a functional ribosomal complex in two steps - first, the formation of the 48S complex from the 43S initiation complex and mRNA followed by its subsequent joining with the 60S subunit, enabling polypeptide chain formation. Of the many steps in translation, the rate-limiting step, initiation, is subjected to the most regulatory control. Many stimuli, such as growth factors and stress, either stimulate or inhibit specific eIFs. Aside from initiation, translation can also be attenuated during elongation. For instance, elevated levels of Ca2+ or cAMP can block the action of eukaryotic elongation factor 2 (eEF2) via AMPK. Finally, upon recognition of a stop codon, eRF1 and eRF3 mediate termination of translation and ribosome disassembly and recycling

Selected Reviews:

• Dever TE, Green R (2012) The elongation, termination, and recycling phases of translation in eukaryotes. Cold Spring Harb Perspect Biol 4(7), a013706.
• Gebauer F, Hentze MW (2004) Molecular mechanisms of translational control. Nat. Rev. Mol. Cell Biol. 5(10), 827–35.
• Hinnebusch AG (2011) Molecular mechanism of scanning and start codon selection in eukaryotes. Microbiol. Mol. Biol. Rev. 75(3), 434–67, first page of table of contents.
• Sonenberg N, Hinnebusch AG (2009) Regulation of translation initiation in eukaryotes: mechanisms and biological targets. Cell 136(4), 731–45.
• Spirin AS (2009) How does a scanning ribosomal particle move along the 5'-untranslated region of eukaryotic mRNA? Brownian Ratchet model. Biochemistry 48(45), 10688–92.
• Steitz TA (2008) A structural understanding of the dynamic ribosome machine. Nat. Rev. Mol. Cell Biol. 9(3), 242–53.

We would like to thank Rachel Wolfson for reviewing this diagram.