Undetected antisense tRNAs in mitochondrial genomes?

Hervé Seligmann

doi:10.1186/1745-6150-5-39

Abstract

BackgroundThe hypothesis that both mitochondrial (mt) complementary DNA strands of tRNA genes code for tRNAs (sense-antisense coding) is explored. This could explain why mt tRNA mutations are 6.5 times more frequently pathogenic than in other mt sequences. Antisense tRNA expression is plausible because tRNA punctuation signals mt sense RNA maturation: both sense and antisense tRNAs form secondary structures potentially signalling processing. Sense RNA maturation processes by default 11 antisense tRNAs neighbouring sense genes. If antisense tRNAs are expressed, processed antisense tRNAs should have adapted more for translational activity than unprocessed ones. Four tRNA properties are examined: antisense tRNA 5' and 3' end processing by sense RNA maturation and its accuracy, cloverleaf stability and misacylation potential.ResultsProcessed antisense tRNAs align better with standard tRNA sequences with the same cognate than unprocessed antisense tRNAs, suggesting less misacylations. Misacylation increases with cloverleaf fragility and processing inaccuracy. Cloverleaf fragility, misacylation and processing accuracy of antisense tRNAs decrease with genome-wide usage of their predicted cognate amino acid.ConclusionsThese properties correlate as if they adaptively coevolved for translational activity by some antisense tRNAs, and to avoid such activity by other antisense tRNAs. Analyses also suggest previously unsuspected particularities of aminoacylation specificity in mt tRNAs: combinations of competition between tRNAs on tRNA synthetases with competition between tRNA synthetases on tRNAs determine specificities of tRNA amino acylations. The latter analyses show that alignment methods used to detect tRNA cognates yield relatively robust results, even when they apparently fail to detect the tRNA's cognate amino acid and indicate high misacylation potential.ReviewersThis article was reviewed by Dr Juergen Brosius, Dr Anthony M Poole and Dr Andrei S Rodin (nominated by Dr Rob Knight).

Highlights

The hypothesis that both mitochondrial complementary DNA strands of tRNA genes code for tRNAs is explored
Because the identity of the antisense anticodon differs in specific species from that found in almost all other species in that group, the results suggest that upon the change in antisense anticodon from the usual antisense anticodon, the signals in the antisense tRNA’s sequence that determine its aminoacylation potential evolved so as to match better the new anticodon
General conclusions The four properties of antisense tRNAs that were explored and are relevant for accurate protein synthesis by such antisense tRNAs (processing, misacylation tendency, cloverleaf stability and the accuracy of processing by sense RNA maturation) are on average inter-related in a way that some antisense tRNAs seem adapted for translational activity

Summary

Introduction

The hypothesis that both mitochondrial (mt) complementary DNA strands of tRNA genes code for tRNAs (sense-antisense coding) is explored. This could explain why mt tRNA mutations are 6.5 times more frequently pathogenic than in other mt sequences. Life history and other fitness-related properties associate with each of these non-coding, yet non-random properties of mRNAs: off frame stop frequency [2,3]; and secondary structure formation [4,5,6,7] These observations suggest that sequences should be considered from a perspective of fulfilling multiple tasks. This is suggested, among others, by complementarities existing between acceptor stems of these tRNA pairs [21]

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