Protein Synthesis -Translation and Regulation

Regulatory features of the 5'UTRs of mRNAs in general involve length, secondary structure, upstream open-reading frames, and specific sequences that interact with RNA binding proteins (). The -splicing processing of many mRNAs results in a relatively short 5'UTR in which the SL is located near the AUG codon (). A few mRNAs, e.g., , contain long 5'UTRs that harbor upstream open-reading frames (), which have a profound effect on translation efficiency in other organisims ().

Mechanism and regulation of eukaryotic protein synthesis.

Figure 1. Complexes formed and factors participating in the initiation of 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.

This review presents a description of the numerous eukaryotic protein synthesis factors and ..
Protein Synthesis and Translational Control

Regulation of protein synthesis during heat shock

Many components of the translational machinery have been identified in , including rRNAs (; ; ), ribosomal proteins (; ; ), 5S RNA (), tRNA (; ; ; ), and aminoacyl tRNA synthetases (; ; ).

Protein synthesis regulation, ..

Translational Control, Protein Synthesis, RNA Regulation …

AB - A variety of factors have been shown to influence rates of protein breakdown in rat skeletal muscles. Muscles isolated from hypophysectomized rats show lower rates of protein synthesis and breakdown than those from normal controls. The lack of growth hormone is primarily responsible for the lower rates of protein synthesis, but this hormone does not affect overal protein catabolism. The lack of thyroid hormones is responsible for reduced protein breakdown in muscle after hypophysectomy or thyroidectomy. Treatment with triiodothyronine or thyroxine stimulates protein breakdown as well as synthesis in muscle after a lag time of 2 days. This acceleration of protein catabolism accounts for the decrease in weight of muscle and liver in hyperthyroidism. Thyroid hormones also increase the content of lysosomal proteases and other hydrolases in muscle and liver, and this effect may be responsible for the concomitant increase in protein breakdown in these tissues. In fasting, proteolysis in muscle rises and protein synthesis falls to provide the organism with amino acid precursors for gluconeogenesis and protein synthesis. However, in muscles of adrenalectomized rats, protein breakdown does not increase and may even decrease on fasting. Consequently these muscles show no net loss of protein content. Treatment of these animals with glucocorticoids leads to an increase in protein breakdown and increased release of amino acids. This effect is evident in muscles of fasted but not fed animals. The ability of glucocorticoids to promote protein catabolism in muscle during fasting complements their actions in stimulating hepatic gluconeogenesis.

Abstract Muscle protein synthesis ..


Although there are many instances in which specific structures in the 3'UTR have been shown to affect translational efficiency in and other organisms (), the molecular interactions responsible for these effects are only partially understood. In oocytes, CPEB binds and sequesters eIF4E through an intermediary protein, Maskin (). In embryos, there is a similar interaction between the 3'UTR-binding factor Smaug and eIF4E, mediated by another protein, Cup (). However, in the translational component(s) involved in GLD-1-mediated regulation remain unknown (; ; ). The other 3'-terminal element, the poly(A) tract, increases the rate of translational initiation in yeast and plants due to the binding of PABP to a specific site near the N-terminus of eIF4G (; ; see ). Poly(A) stabilizes the PABP•eIF4G•eIF4E complex, which in turn leads to enhanced translational re-initiation (). As discussed below, there are several regulatory mechanisms in that involve changing the poly(A) length.