Protein synthesis is one of nature's essential processes consisting of transcription and translation. Translation can be divided into three stages: initiation, elongation, and termination. These schemes are very similar in both eukaryotes and prokaryotes due to the conservation of similar ribosomes. Nevertheless, there are significant differences as seen in the complexity of the eukaryotic initiation complex. The presence of this complexity within the eukaryotic initiation system has been an enigma for scientists to solve throughout the world. The importance of translation initiation is of direct relevance to many disciplines of science and forming a concrete foundation of its complex mechanism is a must. Future discoveries should put all the pieces of this puzzle in order, however presently it is necessary to view these different theories and put them in place. With so many factors and interactions, finding a mechanism for translation initiation seems feeble, however crucial. To begin the discussion of translation initiation, an overview of the process will be mentioned through the links found below, however, our discussion continues below the links.
Translation Initiation in Eukaryotes: Initiation of Protein Synthesis
Ribosomes: Protein Synthesis Factories
Initiation Factors of Protein Synthesis
eIF1A Protein Synthesis Factor
PABP: Poly(A)-Binding Protein Synthesis Factor
Initiation Factors and Capped Mediated 48S Initiation Complex Formation of Protein Synthesis
tRNA Mimicry in Initiation Factors for Protein Synthesis
Initiation Codons in Protein Synthesis
The Scanning Model of Translation Initiation
Leaky Scanning in Protein Synthesis
Reinitiation of Protein Synthesis
Internal ribosome entry sequences (IRESs) and Protein Synthesis
IRES Stimulated Initiation of Protein Synthesis
Regulation of Protein Synthesis
Phosphorylation Regulation of Protein Synthesis
Repression of Translation and Protein Synthesis through 5'-UTR Regulatory Elements
Evolutionary Aspects of Protein Synthesis and Origins of Eukaryotic Initiation Factors
In addition to the complexity of the translation initiation system, fomration of suitable protocols for experimentation was unfortunately rare within translation initiation studies until recently. The use of "reconstituted translation systems" (Kozak 1999), for example purified initiation factors and washed ribosomes, are very low in activity and often many of the protein factors are incomplete. Such limitations had put up a boundary to highly effective experimentation and limited the concrete data available from productive translation initiation studies within eukaryotes.
Nevertheless, the current information present on translation initiation will provide me with the opportunity to discuss the structure and function of ribosomes and protein initiation factors and their proposed role(s) in translation initiation. With this preliminary discussion, the complexity of the translation initiation system can be viewed and certain models of the mechanism of translation initiation can be favored over others. I believe acceptance of any translation initiation model without a full scope of accurate and complete experimental results which currently are not available, would however not seem reasonable.
The purpose of this paper therefore, is to present an accurate picture of the translation initiation process and to validate and differentiate the currently known mechanisms of initiation. The scanning model of translation initiation is the presently favored model, as depicted in its sole presence in the majority of textbooks as the initiation mechanism, due to the abundant evidence to prove its existence. However, controversy has arisen due to the presence of internal ribosome entry sites (IRESs) which promote translation initiation in a diverse mechanism compared to the proposed scanning model. Unfortunately, I cannot propose which mechanism is the "correct" model of eukaryotic translation initiation, because in addition to the lack of complete data, too few experiments have been aimed at resolving the mechanism of initiation, with many at resolving the functions of translation initiation factors.
Our current view of translation initiation, as seen above, greatly lacks the data needed to withstand any concrete theories. Nevertheless, future work in this exciting area of protein synthesis reseach will eventually reveal and test the basic tenets of the proposed initiation factors and the mechanisms of initiation. Every year, the list of initiation factors and their proposed functions seems to be getting longer, depicting a more complex initiation process then previously thought.
With better experimentation protocols and suitable conditions for adequate mRNA leves, I believe that it will hopefully become clearer as to how the process of initiation is accomplished and what roles the scanning model and IRES play. Whether translation initiation is masked by one of these models, or is a fusion of the two lies to be discovered.
In closing, it is just a matter of time with subsequent discoveries, that the pieces of the translation initiation puzzle will slowly be pieced together, thereby revealing another one of nature's best kept secrets to science.