Abstract
Protein synthesis is a fundamental biological mechanism bringing the DNA-encoded genetic information into life by its translation into molecular effectors - proteins. The initiation phase of translation is one of the key points of gene regulation in eukaryotes, playing a role in processes from neuronal function to development. Indeed, the importance of the study of protein synthesis is increasing with the growing list of genetic diseases caused by mutations that affect mRNA translation. To grasp how this regulation is achieved or altered in the latter case, we must first understand the molecular details of all underlying processes of the translational cycle with the main focus put on its initiation. In this review I discuss recent advances in our comprehension of the molecular basis of particular initiation reactions set into the context of how and where individual eIFs bind to the small ribosomal subunit in the pre-initiation complex. I also summarize our current knowledge on how eukaryotic initiation factor eIF3 controls gene expression in the gene-specific manner via reinitiation.
Highlights
Translation is the final step of the Central Dogma in Molecular Biology capturing the flow of genetic information in the cell
We found that the extreme N-terminal domain (NTD) of a/TIF32 and the PCI domain in the c/NIP1-C-terminal domain (CTD) form important intermolecular bridges between eIF3 and the 40S [41,59,117], and that the RNA recognition motif (RRM) of b/PRT1 plays a direct role in anchoring eIF3 to the ribosome [14,17]
The fact that mutating the eIF3-binding site in mammalian eIF4G had no impact on initiation in cells, as mentioned above, and that this mutant form of eIF4GI remained associated with polysomes in siRNA-treated HeLa cells together suggested that the eIF4G–eIF3 interaction may not be essential for association of eIF4F and mRNA with the 43S pre-initiation complex (PIC) in mammalian cells and could be dispensable for basal translation in general [26]
Summary
Translation is the final step of the Central Dogma in Molecular Biology capturing the flow of genetic information in the cell.
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