Transfer RNA recognition by aminoacyl‐tRNA synthetases

Abstract

The aminoacyl-tRNA synthetases are an ancient group of enzymes that catalyze the covalent attachment of an amino acid to its cognate transfer RNA. The question of specificity, that is, how each synthetase selects the correct individual or isoacceptor set of tRNAs for each amino acid, has been referred to as the second genetic code. A wealth of structural, biochemical, and genetic data on this subject has accumulated over the past 40 years. Although there are now crystal structures of sixteen of the twenty synthetases from various species, there are only a few high resolution structures of synthetases complexed with cognate tRNAs. Here we review briefly the structural information available for synthetases, and focus on the structural features of tRNA that may be used for recognition. Finally, we explore in detail the insights into specific recognition gained from classical and atomic group mutagenesis experiments performed with tRNAs, tRNA fragments, and small RNAs mimicking portions of tRNAs.

A recurrent general RNA binding domain appended to plant methionyl-tRNA synthetase acts as a cis-acting cofactor for aminoacylation

“…Basically, aminoacyl‐tRNA synthetases are built around a common architecture: a catalytic domain that interacts with the acceptor stem of tRNA; an anticodon binding domain. Numerous aminoacyl‐tRNA synthetases are able to aminoacylate minihelices derived from the acceptor‐TΨC stem–loop of their corresponding tRNAs (Beuning and Musier‐Forsyth, 1999). Assuming that the very primordial synthetases were solely made of the catalytic domain and catalyzed aminoacylation of acceptor minihelices of tRNA (Schimmel and de Pouplana, 1995), it is tempting to speculate that the interaction between the EMAPII‐like domain of plant MetRS and the acceptor stem of tRNA i Met recapitulates a second stage primitive enzyme with an appended general RNA binding domain that might have improved the proper positioning of the acceptor minihelix in the active site.…”

Origin of the Genetic Code: First Aminoacyl–tRNA Synthetases Could Replace Isofunctional Ribozymes When Only the Second Base of Codons Was Established

“…This operational code or "supercode" (Weiss and Buchanan, 2005) has a history of long idiosyncratic coevolution of tRNA-aaRS pairs and apparently is not quite as universal as the "classic" code (Beuning and Musier-Forsyth, 1999). At the same time, many arguments point to this "secondary" tRNA supercode being older, and possibly of a more fundamental nature, than the classic code (Schimmel et al, 1993;Rodin et al, 1996;Rodin and Ohno, 1997).…”

The Codes of Life

“…This rationale incorporates the earlier studies of Miller et al (1981) and Yamane et al (1981), showing that dimers could be regulatory to protein synthesis, modulating the availability of tRNAs for translation, and of Smith and Yarus (1989), showing that the neighbor tRNAs in the P and A sites of ribosomes interact side by side via the bases lateral to the anticodons in the loop, which is considered a different kind of dimer. The non-ribosomal dimer-directed transferase activity could be experimentally tested, either utilizing present day tRNAs (possibly too large and rigid for facilitating the reaction) or the various kinds of mini-tRNAs that have been used as acceptors for the aRS function or for spontaneous aminoacylation (see Beuning and Musier-Forsyth, 1999), but containing anticodon-like loops, able to dimerize.…”