Mechanism and regulation of eukaryotic protein synthesis.
and unique regulation of the synthesis of the ..
represents an especially favorable system to study the extraordinarily complicated process of eukaryotic protein synthesis, which involves over 100 RNAs and over 200 polypeptides just for the core machinery. The first decades of research in eukaryotic protein synthesis relied on fractionated mammalian and plant systems, with little or no input of genetics. This began to change in the 1970's when the powerful genetics of was brought to bear on central questions in protein synthesis. From this research came important new insights for translation in all eukaryotes, including discovery of the initiation codon scanning mechanism (), new protein synthesis factors and regulatory kinases (), previously unknown interactions among initiation factors (), the core structure of eIF3, the most complex of the initiation factors (), and new regulatory pathways for the control of protein synthesis (). , however, has many features of higher eukaryotes that are shared by yeast, , tissues, organs, muscles, a nervous system, developmental stages, cell lineages, ., which involve processes regulated at the translational level. Furthermore, signaling pathways leading to protein synthesis are considerably more similar between and humans than between yeast and humans. Thus, allows protein synthesis researchers to combine biochemistry, cell biology, genetics, and genomics to understand fundamental questions about the regulation of gene expression at the translational level.
Regulation of protein synthesis by insulin
From studies in mammals, yeasts, and plants, it is known that the three steps of protein synthesis are catalyzed by three groups of proteins: initiation, elongation, and release factors (). A different class of initiation factors (eIF1, eIF2, etc.) catalyzes each step of initiation (). [A uniform nomenclature system for translation factors is used here ()]. A ternary complex of eIF2•GTP•Met-tRNAi binds to the 40S ribosomal subunit to form the 43S initiation complex. Recruitment of mRNA to the 43S initiation complex to form the 48S initiation complex requires eIF3, the poly(A)-binding protein (PABP), and the eIF4 proteins. eIF3 is a ~800-kDa multimer that is also required for Met-tRNAi binding to the 40S subunit (molecular masses refer to the mammalian factors). PABP is a 70-kDa protein that specifically binds poly(A) and homo-oligomerizes. The eIF4 factors consist of: eIF4A, a 46-kDa RNA helicase; eIF4B, a 70-kDa RNA-binding and RNA-annealing protein; eIF4H, a 25-kDa protein that acts with eIF4B to stimulate eIF4A helicase activity; eIF4E, a 25-kDa cap-binding protein; and eIF4G, a 185-kDa protein that specifically binds to and co-localizes all of the other proteins involved in mRNA recruitment on the 40S subunit.