Amino acid modifications on tRNA<xref xml:base="fn" rid="fn1">†</xref>

Abstract

The accurate formation of cognate aminoacyl-tRNAs (aa-tRNAs) is essential for the fidelity of translation. Most amino acids are esterified onto their cognate tRNA isoacceptors directly by aminoacyl-tRNA synthetases (aaRSs). However, in the case of four amino acids (Gln, Asn, Cys and Sec), aminoacyl-tRNAs are made through indirect pathways in many organisms across all three domains of life. The process begins with the charging of noncognate amino acids to tRNAs by a specialized synthetase in the case of Cys-tRNACys formation or by synthetases with relaxed specificity such as the non-discriminating glutamyl-tRNA synthetase (ND-GluRS), non-discriminating aspartyl-tRNA synthetase (ND-AspRS) and seryl-tRNA synthetase (SerRS). The resulting misacylated tRNAs are then converted to cognate pairs through transformation of the amino acids on the tRNA, which is catalyzed by a group of tRNA-dependent modifying enzymes such as tRNA-dependent amidotransferases, Sep-tRNA:Cys-tRNA synthase (SepCysS), O-phosphoseryl-tRNA kinase (PSTK) and Sep-tRNA:Sec-tRNA synthase (SepSecS). The majority of these indirect pathways are widely spread in all domains of life and thought to be ancient in the course of evolution.

Transfer RNA: A dancer between charging and mis-charging for protein biosynthesis

“…In contrast, its counterparts in some bacteria (e.g., E. coli) and all eukaryotes (e.g., human beings) encode a discriminating GluRS unable to recognize and charge tRNA Gln . In these cases, GlnRSs are also encoded [7]. The produced Glu-tRNA Gln is not transported to the EF-Tu/ribosome machinery.…”

“…The central role of tRNA is to establish genetic code by coupling an mRNA codon with an amino acid [1,2]. Besides this canonical function, it also carries out a wide range of non-aminoacylation functions such as cell wall biosynthesis, anti-biotic synthesis, protein degradation, bacterial membrane lipid modification, virus replication, apoptosis, amino acid biosynthesis, and precursor of small regulatory RNA, which are collectively designated non-canonical functions and have been previously reviewed elsewhere [3][4][5][6][7][8]. …”

Distinct genetic code expansion strategies for selenocysteine and pyrrolysine are reflected in different aminoacyl‐tRNA formation systems

“…Sec biosynthesis in all domains of life is achieved by RNA‐dependent amino acid modification. As such it is reminiscent of other pathways of tRNA‐dependent amino acid synthesis that form Asn‐tRNA, Gln‐tRNA and Cys‐tRNA in many organisms [32]. The individual reactions in this stepwise process may actually be carried out in a large tRNA:protein complex.…”

Inhibition of Helicobacter pylori Glu‐tRNAGln amidotransferase by novel analogues of the putative transamidation intermediate

“…In about half of the bacterial and archaeal species whose genomes have been sequenced, Asn-tRNA Asn synthesis is catalysed Abbreviations aa-tRNA, aminoacyl-tRNA; AdT, Glu-tRNA Gln amidotransferase; DMF, N, N-dimethylformamide; EDC, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride; GatCAB, trimeric AdT; GluRS, glutamyl-tRNA synthetase; MHB, Mueller-Hinton broth; SE, standard error. by a similar indirect pathway involving the same AdT [5,6].…”

“…1). by a similar indirect pathway involving the same AdT [5,6]. Second, a Glu-tRNA Gln amidotransferase (AdT) transamidates it into Gln-tRNA Gln which is then recognized by the elongation factor EF-Tu, allowing its participation to protein biosynthesis on the ribosome.…”