Aminoacyl-tRNAs: setting the limits of the genetic code

  1. Michael Ibba1,3 and
  2. Dieter Söll2,4
  1. 1Department of Microbiology, The Ohio State University, Columbus, Ohio 43210-1292, USA; 2Departments of Molecular Biophysics and Biochemistry, and Chemistry, Yale University, New Haven, Connecticut 06520-8114, USA

This extract was created in the absence of an abstract.

Aminoacyl-tRNAs (aa-tRNAs) are simple molecules with a single purpose—to serve as substrates for translation. They consist of mature tRNAs to which an amino acid has been esterified at the 3′-end. The 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases (aaRSs, of which there are two classes), one for each amino acid of the genetic code (Ibba and Söll 2000). This would be fine if it were not for the fact that such a straightforward textbook scenario is not true in a single known living organism. aa-tRNAs lie at the heart of gene expression; they interpret the genetic code by providing the interface between nucleic acid triplets in mRNA and the corresponding amino acids in proteins. The synthesis of aa-tRNAs impacts the accuracy of translation, the expansion of the genetic code, and even provides tangible links to primary metabolism. These central roles vest immense power in aa-tRNAs, and recent studies show just how complex and diverse their synthesis is.

How many aa-tRNAs are there?

The aa-tRNAs typically found in the cell can be divided into three main types (Table 1). The largest group comprises correct pairings of an amino acid and the corresponding tRNA, and they serve as substrates for ribosomal translation. Among these, the canonical elongator tRNAs are by far the most common. They are usually made directly by the corresponding aaRS (Woese et al. 2000; O'Donoghue and Luthey-Schulten 2003), and then screened for correctness by elongation factor Tu (EF-Tu), which also delivers them to the ribosome (LaRiviere et al. 2001). In much the same way, initiator aa-tRNAs in archaea and eukaryotes are made directly by methionyl-tRNA synthetase (MetRS), and then bind to initiation factors that deliver them to the ribosome. In bacteria and organelles the situation is more complex, as the Met-tRNAfMet produced by MetRS must first …

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