Role of the Initiation Factors in mRNA Start Site Selection and fMet‐tRNA Recruitment by Bacterial Ribosomes

Abstract

Translation initiation is a complex, multi‐step process of fundamental importance in all kingdoms of life, during which the start site of the genetic message transmitted in the form of an RNA molecule (mRNA) is selected, and the level of translation determined. Being the slowest step of protein synthesis, initiation is the phase most often subject to regulation. Here we review, in a historical perspective and focusing mainly on results from our laboratory, the development of our perception of the mechanisms by which the most relevant steps of this pathway occur in bacteria. In particular, we describe: (a) the mechanistics and kinetics of translation initiation; (b) properties of mRNAs with and without Shine–Dalgarno sequence relevant for initiation site selection and translational efficiency; c) ribosomal binding and dissociation of the initiation factors, formation and properties of translation initiation intermediates; (d) the mechanisms by which translation initiation fidelity is ensured. Finally, we provide a short survey of the known translation initiation inhibitors.

Translation initiation factor 3 families: what are their roles in regulating cyanobacterial and chloroplast gene expression?

“…The discovery that cyanobacteria and photosynthetic eukaryotes have multiple IF3s adds an interesting, new layer of complexity to translation initiation in these organisms by expanding the possible roles of IF3s (Gualerzi et al 2010) as regulators of gene expression (Gutu et al 2013). How such regulation is achieved mechanistically is an important question, and the models presented in this review hopefully will help to guide such studies.…”

Haloferax volcanii, a Prokaryotic Species that Does Not Use the Shine Dalgarno Mechanism for Translation Initiation at 5′-UTRs

“…However, in recent years it became evident that translation initiation in prokaryotes might be more complex, that additional translation initiation mechanisms exist, and that the results obtained with E. coli cannot be extrapolated to all bacteria or all prokaryotes [15] – [17] . An extensive analysis of 141 bacterial and 21 archaeal genomes revealed a high divergence of the occurrences of SD motifs.…”

Structural Dynamics of Bacterial Translation Initiation Factor IF2

“…adjusted in the peptidyltransferase center of the ribosome for the first transpeptidation reaction (1)(2)(3). The 70 S IC is assembled in two steps.…”