Translation aminoacyl-tRNA synthetases

Translator. Aminoacyl-tRNA synthetases are the only component of gene expression that decodes the genetic code. Explain. 

A detailed treatment of the evolution of the genetic code requires modelling physical components of the translational process this includes the dynamic processes of the tRNAs and the aminoacyl-tRNA synthetases (Vetsigian et al., 2006). Thus, in spite of considerable advances in the search for the roots of the genetic code, there is still much to do ... 

R. Chenevert S. Bernier J. Lapointe, Inhibitors of Aminoacyl-tRNA Synthetases as Antibiotics and Tools for Structural and Mechanistic Studies. In Translation Mechanisms J. Lapointe, L. Brakier-Gingras, Eds. Eurekah.com/Landes Bioscience and Kluwer Academic/Plenum Publishers Georgetown TX, 2003 pp 416-428. 

Aminoacyl-tRNA synthetases charge the appropriate tRNA with the correct amino acid, which is important in maintaining the fidelity of protein translation. To genetically encode an unnatural amino acid, the substrate specificity of the orthogonal synthetase needs to be altered to charge the orthogonal tRNA with only the desired unnatural amino acid and none of the common 20 amino acids. A general scheme was developed for... 

Building on earlier work of Osawa and co-workers [55], Oliver and Kowal [52] tested the feasibility of introducing a noncoded amino acid at an unassigned codon in M. luteus. DNA templates were prepared which coded for 19-mer polypeptides containing either the unassigned codon AGA(Arg) or the termination codon TAG at position 13 under the control of a T7 RNA polymerase promoter. The corresponding tRNAs, produced as described in Sect. 2, were based on tRNA and acylated with phenylalanine. The tRNA was modified to prevent recognition by the alanine aminoacyl-tRNA synthetase and to increase translational efficiency. 

The translation of the mRNA into proteins is the final step in the biological flow of information (see Fig. 6.1). Similar to other macromolecular polymerizations, protein synthesis can be divided into initiation, chain elongation, and termination. Critical players in this process are the aminoacyl transfer RNAs (tRNAs). These molecules form the interface between the mRNA and the growing polypeptide. Activation of tRNA involves the addition of an amino acid to its acceptor stem, a reaction catalyzed by an aminoacyl-tRNA synthetase. Each aminoacyl-tRNA synthetase is highly specific for one amino acid and its corresponding tRNA molecule. The anticodon loop of each aminoacyl-tRNA interacts... 

Terms in bold are defined aminoacyl-tRNA 1035 aminoacyl-tRNA synthetases 1035 translation 1035 codon 1035 reading frame 1036 initiation codon 1038 termination codons 1038 open reading frame (ORF) 1039 anticodon 1039 wobble 1041... 

As any elementary textbook on molecular biology will relate, the sequences of proteins are stored in DNA in the form of a triplet code. Each amino acid is encoded by one or more triplet combinations of the four bases A, T, G, and C. For example, tryptophan is coded by the sequence TGG. The sequence of triplets is converted into a protein by a process in which DNA is first transcribed into mRNA. This message is then translated into protein on the ribosomes in conjunction with tRNA and the aminoacyl-tRNA synthetases. In prokaryotes, there is a one-to-one relationship between the sequence of triplets in the DNA. and the sequence of amino acids in the protein. In eukaryotes, the DNA often contains stretches of intervening sequences or introns which are excised from the mRNA after transcription (Chapter 1). 

Aminoacyl-tRNA synthetases (aaRSs) are critical components of the translation machinery for protein synthesis in every living cell (1). Each aaRS enzyme in this family links a single amino acid covalently to one or more tRNA isoacceptors to form charged tRNAs. Identity elements within the tRNAs serve as molecular determinants or antideterminants that aid in selection by cognate aaRSs (2). Some aaRSs also have an amino acid editing mechanism to clear their mistakes (3). The canonical aaRSs and aaRS-like proteins have functionally diverged to perform many other important roles in the cell (4, 5). Their versatility and adaptability have provided unique opportunities to develop biotechnology tools and to advance medical research. 

Hendrickson T, Schimmel P. Transfer RNA-dependent amino acid discrimination by aminoacyl-tRNA synthetases. In Translation Mechanisms. Lapointe J, Brakier-Gingras L, eds. 2003. Kluwer Academic/Plenum Publishers, New York. p. 34-64. 

Tsao ML, Tian F, Schultz P. Incorporation of unnatural reactive amino acids into phage display libraries using ortiiogonal mutant aminoacyl-tRNA synthetases for post-translational modification. PCT Int. Appl. 2007 114. 

Aminoacyl tRNA Synthetases, Chemistry of Translation Topics in Chemical Biology Phage Display... 

How do synthetases choose their tRNA partners This enormously important step is the point at which "translation" takes place—at which the correlation between the amino acid and the nucleic acid worlds is made. In a sense, aminoacyl-tRNA synthetases are the only molecules in biology that "know" the genetic code. Their precise recognition of tRNAs is as important for high-fidelity protein synthesis as is the accurate selection of amino acids. 

Protein synthesis is called translation because information present as a nucleic acid sequence is translated into a different language, the sequence of amino acids in a protein. This complex process is mediated by the coordinated interplay of more than a hundred macromolecules, including mRNA, rRNAs, tRNAs, aminoacyl-tRNA synthetases, and protein factors. Given that proteins typically comprise from 100 to 1000 amino acids, the frequency at vchich an incorrect amino acid is incorporated in the course of protein synthesis must be less than 10 4. Transfer RNAs are the adaptors that make the link betvceen a nucleic acid and an amino acid. These molecules, single chains of about 80 nucleotides, have an L-shaped structure. 

Protein synthesis is called Lranslalioii because information present as a nucleic acid sequence is translated into a different language, the sequence of amino acids in a protein. This complex process is mediated by the coordinated interplay of inore than a hundred macro molecules, including mRNA, rRNAs, tRNAs, aminoacyl-tRNA synthetases,... 

An RNA aptamer has been selected to activate the carboxylic acid of amino acids that mimics the formation of a mixed phosphate anhydride synthesis of aminoacyl tRNA synthetases. The optimal aptamer requires only Ca + for the reaction, and operates at low pH with Xm 50 mM and /ccat 1.1 min for the activation of leucine. This lends support to the concept of translation in an RNA-based world. An RNA-cleaving DNAzyme has been used to target a chemokine receptor required by HIV-1 for entry into susceptible cells. The DNAzyme was found to be very efficient, and specifically interfered with the fusion of cells that harboured the T-lymphocytotropic HIV-1 envelope. 

Lapointe, J. Giegd, R. (1991). Transfer RNAs and aminoacyl-tRNA synthetases. In Translation in Eukaryotes. (Trachsel, H., ed.), pp. 35-69, CRC Press, Boca Raton. 

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