Disease relevance of Genetic Code

• The genetic code in a eukaryotic system has been expanded by the engineering of Escherichia coli tyrosyl-tRNA synthetase (TyrRS) with the Y37V and Q195C mutations (37V195C), which specifically recognize 3-iodo-L-tyrosine rather than L-tyrosine [1].

High impact information on Genetic Code

• To overcome the biochemical defect, we expressed wildtype ATPase 6 protein allotopically from nucleus-transfected constructs encoding an amino-terminal mitochondrial targeting signal appended to a recoded ATPase 6 gene (made compatible with the universal genetic code) that also contained a carboxy-terminal FLAG epitope tag [2].
• It has previously been proposed that in plant mitochondria there is a departure from the universal genetic code, with CGG specifying tryptophan instead of arginine [3].
• The arginine site can be placed within the G site by structural homology, with consequent implications for RNA-amino acid interaction, for the origin of the genetic code, for control of RNA activities, and for further catalytic capabilities for RNA [4].
• Average amounts of lysine, aspartic acid, glutamic acid, and alanine are above the levels anticipated from the genetic code, and arginine, serine, leucine, cysteine, proline, and histidine are below such levels [5].
• Early work on aminoacylation of alanine-specific tRNA (tRNA(Ala)) by alanyl-tRNA synthetase (AlaRS) gave rise to the concept of an early "second genetic code" imbedded in the acceptor stems of tRNAs [6].

Chemical compound and disease context of Genetic Code

• Reassigning cysteine in the genetic code of Escherichia coli [7].
• This is the first example from nature of direct aminoacylation of a tRNA with a non-canonical amino acid and shows that the genetic code of E. coli can be expanded to include UAG-directed pyrrolysine incorporation into proteins [8].

Biological context of Genetic Code

• The Curation program contains prior knowledge of the genetic code and of the PAX6 gene including cDNA sequence, location of intron/exon boundaries, and protein domains, so that the minimum of information need be provided by the submitter or Curator [9].
• These results are best explained by the presence of nonfunctional duplications of a portion of the mtDNA, probably located in the nuclear genome, since transfer into the nuclear gene would render the COI gene nonfunctional due to differences in the nuclear and mitochondrial genetic codes [10].
• To maintain the correct Watson-Crick base pairing properties of the wobble base (and hence proper translation of the genetic code), TGT must recognize its heterocyclic substrate with high specificity [11].
• By using the established amino acid sequence of the IF2 H-chain and a knowledge of the genetic code, 14 oligonucleotides were assigned within the constant region and four within the variable region of the IF2 H-chain [12].
• It uses the "mitochondrial" genetic code, i.e., it contains a TGA codon, whereas all other protein-encoding genes, and all but one intronic open reading frame, use the "standard" genetic code (UGG for tryptophan) [13].

Anatomical context of Genetic Code

• Recent sequence analysis of human mtDNA suggests that the genetic code used by mammalian mitochondria deviates in a number of respects from the 'universal' code, the most striking of these being the use of the UGA termination codon to specify tryptophan [14].

Associations of Genetic Code with chemical compounds

• In this way, CGG codons can be changed to UGG codons in the mRNA so that tryptophan may be encoded according to the universal genetic code [3].
• RNA helical oligonucleotides that recapitulate the acceptor stems of transfer RNAs, and that are devoid of the anticodon trinucleotides of the genetic code, are aminoacylated by aminoacyl tRNA synthetases [15].
• In considering evolutionary mechanisms for this curious divergence from the standard genetic code, we propose the existence of progenitor tRNAs for glutamine that can weakly suppress UAA and UAG codons [16].
• Nonorthologous replacement of lysyl-tRNA synthetase prevents addition of lysine analogues to the genetic code [17].
• The variations at these two positions and phylogenetic analyses based on the structural information suggest that, in contrast to many other amino acids, discrimination of tyrosine from tryptophan occurred late in the development of the genetic code [18].

Gene context of Genetic Code

• The universal genetic code is used in both the ND1 and RTL genes; however, the latter is distinguished from the other protein coding genes of C. reinhardtii mtDNA by several characteristics which suggest that RTL may be a more recently acquired gene [19].
• Mice with the NK1 receptor deleted from their genetic code also have an increased firing rate of 5-HT neurons [20].
• In human ND2, the amino-terminal methionine is encoded by AUU, which, as in the "universal" genetic code, is also used as an isoleucine codon in elongation [21].
• The statistical distribution of mutational likelihoods was as predicted on the basis of the PROC cDNA sequence alone, allowing however for the redundancy of the genetic code [22].
• AARS catalyse the attachment of amino acids to transfer RNAs and thereby establish the rules of the genetic code by virtue of matching the nucleotide triplet of the anticodon with its cognate amino acid [23].

Analytical, diagnostic and therapeutic context of Genetic Code

• The expanded genetic code in combination with site-directed mutagenesis was used to probe spectroscopic and structural roles of tryptophan (Trp) residues in Aequorea victoria green fluorescent proteins (avGFPs) [24].

References