TRNA Modification and Genetic Code Variations in Animal Mitochondria

Kimitsuna Watanabe,Shin-Ichi Yokobori

doi:10.4061/2011/623095

Abstract

In animal mitochondria, six codons have been known as nonuniversal genetic codes, which vary in the course of animal evolution. They are UGA (termination codon in the universal genetic code changes to Trp codon in all animal mitochondria), AUA (Ile to Met in most metazoan mitochondria), AAA (Lys to Asn in echinoderm and some platyhelminth mitochondria), AGA/AGG (Arg to Ser in most invertebrate, Arg to Gly in tunicate, and Arg to termination in vertebrate mitochondria), and UAA (termination to Tyr in a planaria and a nematode mitochondria, but conclusive evidence is lacking in this case). We have elucidated that the anticodons of tRNAs deciphering these nonuniversal codons (tRNATrp for UGA, tRNAMet for AUA, tRNAAsn for AAA, and tRNASer and tRNAGly for AGA/AGG) are all modified; tRNATrp has 5-carboxymethylaminomethyluridine or 5-taurinomethyluridine, tRNAMet has 5-formylcytidine or 5-taurinomethyluridine, tRNASer has 7-methylguanosine and tRNAGly has 5-taurinomethyluridine in their anticodon wobble position, and tRNAAsn has pseudouridine in the anticodon second position. This review aims to clarify the structural relationship between these nonuniversal codons and the corresponding tRNA anticodons including modified nucleosides and to speculate on the possible mechanisms for explaining the evolutional changes of these nonuniversal codons in the course of animal evolution.

Highlights

Up to now six codons have been known which are deciphered by the corresponding tRNAs as amino acids different from those assigned by the universal genetic code in animal mitochondria (Figure 1) [1]
The wobble pairings as inferred from the above-expanded wobble rule were confirmed by an in vitro translation system of animal mitochondria, in which in vitro translation was performed by E. coli or bovine mt translation system using synthetic polyribonucleotide made of a series of nonuniversal codon as a messenger, and incorporation of a certain amino acid corresponding to the nonuniversal codon was identified [13, 14]
In the forth step, the wobble pairings were confirmed by an in vitro experiment, in which natural mRNA including a specific codon which was replaced with a certain nonuniversal codon was translated in vitro, and the mRNA activity was detected by enzymatic activity if the mRNA encodes a certain enzyme such as dihydrofolate reductase (DHFR) (Hanada, T., Suzuki, T. and Watanabe, K., unpublished results)

Summary

Introduction

Up to now six codons have been known which are deciphered by the corresponding tRNAs as amino acids different from those assigned by the universal genetic code in animal mitochondria (Figure 1) [1]. We summarize mostly the results obtained in the second step, together with a few cases in the third step, and inquire into the nature of codon-anticodon interaction in the mt translation process and the relationship between nonuniversal genetic code and modified nucleoside in the tRNA anticodon deciphering the codon, during the course of animal evolution. These studies may lead to the understanding as to how the genetic code evolves and how mt tRNAs keep up with the genetic code variations by providing modification at the anticodon of tRNAs. It is important to consider the involvement of aminoacyl-tRNA synthetase (aaRS) in the recognition of tRNA, especially in the case when aaRS recognizes the anticodon region of tRNA as the identity determinant. Since a few cases have been known about the animal mt aaRSs, some discussions will be added in the applicable sections, about the recognition mechanisms of aaRSs toward the corresponding tRNAs involved in the genetic code variations

Genetic Code Variations and the Anticodon Structure of the Corresponding tRNA

H CO N f5C

Conclusion