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      Initiation of mRNA translation in bacteria: structural and dynamic aspects

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          Abstract

          Initiation of mRNA translation is a major checkpoint for regulating level and fidelity of protein synthesis. Being rate limiting in protein synthesis, translation initiation also represents the target of many post-transcriptional mechanisms regulating gene expression. The process begins with the formation of an unstable 30S pre-initiation complex (30S pre- IC) containing initiation factors (IFs) IF1, IF2 and IF3, the translation initiation region of an mRNA and initiator fMet-tRNA whose codon and anticodon pair in the P-site following a first-order rearrangement of the 30S pre- IC produces a locked 30S initiation complex (30S IC); this is docked by the 50S subunit to form a 70S complex that, following several conformational changes, positional readjustments of its ligands and ejection of the IFs, becomes a 70S initiation complex productive in initiation dipeptide formation. The first EF-G-dependent translocation marks the beginning of the elongation phase of translation. Here, we review structural, mechanistic and dynamical aspects of this process.

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          Most cited references163

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          Regulation of bacterial gene expression by riboswitches.

          Riboswitches are structured domains that usually reside in the noncoding regions of mRNAs, where they bind metabolites and control gene expression. Like their protein counterparts, these RNA gene control elements form highly specific binding pockets for the target metabolite and undergo allosteric changes in structure. Numerous classes of riboswitches are present in bacteria and they comprise a common and robust metabolite-sensing system.
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            Lost in translation: the influence of ribosomes on bacterial mRNA decay.

            The lifetimes of bacterial mRNAs are strongly affected by their association with ribosomes. Events occurring at any stage during translation, including ribosome binding, polypeptide elongation, or translation termination, can influence the susceptibility of mRNA to ribonuclease attack. Ribosomes usually act as protective barriers that impede mRNA cleavage, but in some instances they can instead trigger the decay of the mRNA to which they are bound or send a signal that leads to widespread mRNA destabilization within a cell. The influence of translation on mRNA decay provides a quality-control mechanism for minimizing the use of poorly or improperly translated mRNAs as templates for the production of abnormal proteins that might be toxic to bacteria.
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              Metabolic costs of amino acid and protein production in Escherichia coli.

              Escherichia coli is the most popular microorganism for the production of recombinant proteins and is gaining increasing importance for the production of low-molecular weight compounds such as amino acids. The metabolic cost associated with the production of amino acids and (recombinant) proteins from glucose, glycerol and acetate was determined using three different computational techniques to identify those amino acids that put the highest burden on the biosynthetic machinery of E. coli. Comparing the costs of individual amino acids, we find that methionine is the most expensive amino acid in terms of consumed mol of ATP per molecule produced, while leucine is the most expensive amino acid when taking into account the cellular abundances of amino acids. Moreover, we show that the biosynthesis of a large number of amino acids from glucose and particularly from glycerol provides a surplus of energy, which can be used to balance the high energetic cost of amino acid polymerization. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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                Author and article information

                Contributors
                +39 (0)737403240 , claudio.gualerzi@unicam.it
                +39 (0)737403240 , cynthia.pon@unicam.it
                Journal
                Cell Mol Life Sci
                Cell. Mol. Life Sci
                Cellular and Molecular Life Sciences
                Springer Basel (Basel )
                1420-682X
                1420-9071
                11 August 2015
                11 August 2015
                2015
                : 72
                : 22
                : 4341-4367
                Affiliations
                Laboratory of Genetics, University of Camerino, 62032 Camerino, Italy
                Article
                2010
                10.1007/s00018-015-2010-3
                4611024
                26259514
                aa39d745-a93a-41ad-8673-d16bd6103909
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 1 June 2015
                : 28 July 2015
                : 30 July 2015
                Categories
                Review
                Custom metadata
                © Springer Basel 2015

                Molecular biology
                protein synthesis,translation initiation factors,mrna initiation region,fmet-trna,gtp

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