From one amino acid to another: tRNA-dependent amino acid biosynthesis

• Published in: Nucleic acids research Vol. 36; no. 6; pp. 1813 - 1825
• Main Authors: Sheppard, Kelly, Yuan, Jing, Hohn, Michael J, Jester, Brian, Devine, Kevin M, Söll, Dieter
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.04.2008; Oxford Publishing Limited (England)
• Subjects: Amino Acyl-tRNA Synthetases - chemistry; Amino Acyl-tRNA Synthetases - metabolism; Asparagine - biosynthesis; BASIC BIOLOGICAL SCIENCES; Biochemistry & Molecular Biology; Cysteine - biosynthesis; Glutamine - biosynthesis; Nitrogenous Group Transferases - chemistry; Nitrogenous Group Transferases - metabolism; Nucleic Acid Enzymes; Phosphotransferases - chemistry; Phosphotransferases - metabolism; RNA, Transfer, Amino Acyl - metabolism; Selenocysteine - biosynthesis
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkn015

Aminoacyl-tRNAs (aa-tRNAs) are the essential substrates for translation. Most aa-tRNAs are formed by direct aminoacylation of tRNA catalyzed by aminoacyl-tRNA synthetases. However, a smaller number of aa-tRNAs (Asn-tRNA, Gln-tRNA, Cys-tRNA and Sec-tRNA) are made by synthesizing the amino acid on the tRNA by first attaching a non-cognate amino acid to the tRNA, which is then converted to the cognate one catalyzed by tRNA-dependent modifying enzymes. Asn-tRNA or Gln-tRNA formation in most prokaryotes requires amidation of Asp-tRNA or Glu-tRNA by amidotransferases that couple an amidase or an asparaginase to liberate ammonia with a tRNA-dependent kinase. Both archaeal and eukaryotic Sec-tRNA biosynthesis and Cys-tRNA synthesis in methanogens require O-phosophoseryl-tRNA formation. For tRNA-dependent Cys biosynthesis, O-phosphoseryl-tRNA synthetase directly attaches the amino acid to the tRNA which is then converted to Cys by Sep-tRNA: Cys-tRNA synthase. In Sec-tRNA synthesis, O-phosphoseryl-tRNA kinase phosphorylates Ser-tRNA to form the intermediate which is then modified to Sec-tRNA by Sep-tRNA:Sec-tRNA synthase. Complex formation between enzymes in the same pathway may protect the fidelity of protein synthesis. How these tRNA-dependent amino acid biosynthetic routes are integrated into overall metabolism may explain why they are still retained in so many organisms.