Directed Mutations Recode Mitochondrial Genes: From Regular to Stopless Genetic Codes

Mitochondrial genetic codes evolve as side effects of stop codon ambiguity: suppressor tRNAs with anticodons translating stops transform genetic codes to stopless genetic codes. This produces peptides from frames other than regular ORFs, potentially increasing protein numbers coded by single sequences. Previous descriptions of marine turtle Olive Ridley mitogenomes imply directed stop-depletion of noncoding +1 gene frames, stop-creation recodes regular ORFs to stopless genetic codes. In this analysis, directed stop codon depletion in usually noncoding gene frames of the spiraling whitefly Aleurodicus dispersusʼ mitogenome produces new ORFs, introduces stops in regular ORFs, and apparently increases coding redundancy between different gene frames. Directed stop codon mutations switch between peptides coded by regular and stopless genetic codes. This process seems opposite to directed stop creation in HIV ORFs within genomes of immunized elite HIV controllers. Unknown DNA replication/edition mechanisms probably direct stop creation/depletion beyond natural selection on stops. Switches between genetic codes regulate translation of different gene frames

Do anticodons of misacylated tRNAs preferentially mismatch codons coding for the misloaded amino acid?

<p>Abstract</p> <p>Background</p> <p>Accurate amino acid insertion during peptide elongation requires tRNAs loaded by cognate amino acids and that anticodons match codons. However, tRNA misloading does not necessarily cause misinsertions: misinsertion is avoided when anticodons mismatch codons coding for misloaded amino acids.</p> <p>Presentation of the hypothesis</p> <p>Occasional compensation of misacylation by codon-anticodon mismatch necessarily occurs. Putatively, occasional error compensation may be enhanced beyond the random combination of independent errors in tRNA loading and codon-anticodon interactions: tRNA misacylation might alter potentials for codon-anticodon mismatches, perhaps specifically increasing potentials for mismatching those codons coding for the misacylated non-cognate amino acid. This hypothetical phenomenon is called 'error coordination', in distinction from 'error compensation' that assumes independence between misacylation and mismatch.</p> <p>Testing the hypothesis</p> <p>Eventually, the hypothesis should be tested for each combination of amino acid misacylation and codon-anticodon mismatch, by comparing stabilities or frequencies of mismatched codon-anticodon duplexes formed by tRNAs loaded by their cognate amino acid with stabilities formed by that tRNA when misloaded with the amino acid coded by the mismatched codon. Competitive mismatching experiments between misloaded and correctly loaded tRNAs could also be useful, yet more sophisticated experiments.</p> <p>Implications of the hypothesis</p> <p>Detecting error coordination implies estimating error compensation, which also promotes protein synthesis accuracy. Hence even in the absence of evidence for error coordination, experiments would yield very useful insights into misacylation and mismatch processes. In case experiments consider post-transcriptional RNA modifications (especially at wobble positions), results on codon-anticodon mismatches would enable significant improvements and sophistications of secondary structure prediction softwares. Positive results would show that protein translation enhances accuracies of products, not of single steps in the production. Ancient translational machineries putatively optimized error coordination, especially before tRNA editing by tRNA synthetases evolved: few primitive, but functionally versatile tRNA species perhaps executed low accuracy translation. Systems artificially designed/selected for low complexity and high efficiency could make use of this property for anticodons with high levels of error compensation and coordination.</p

Undetected antisense tRNAs in mitochondrial genomes?

<p>Abstract</p> <p>Background</p> <p>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. 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.</p> <p>Results</p> <p>Processed 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.</p> <p>Conclusions</p> <p>These 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.</p> <p>Reviewers</p> <p>This article was reviewed by Dr Juergen Brosius, Dr Anthony M Poole and Dr Andrei S Rodin (nominated by Dr Rob Knight).</p

SARS-CoV-2 and miRNA-like inhibition power

(1) Background: RNA viruses and especially coronaviruses could act inside host cells not only by building their own proteins, but also by perturbing the cell metabolism. We show the possibility of miRNA-like inhibitions by the SARS-CoV-2 concerning for example the hemoglobin and type I interferons syntheses, hence highly perturbing oxygen distribution in vital organs and immune response as described by clinicians; (2) Methods: We compare RNA subsequences of SARS-CoV-2 protein S and RNA-dependent RNA polymerase genes to mRNA sequences of beta-globin and type I interferons; (3) Results: RNA subsequences longer than eight nucleotides from SARS-CoV-2 genome could hybridize subsequences of the mRNA of beta-globin and of type I interferons; (4) Conclusions: Beyond viral protein production, Covid-19 might affect vital processes like host oxygen transport and immune response.Comment: 14 pages, 12 figure

Swinger RNAs in the Human Mitochondrial Transcriptome

Transcriptomes include coding and non-coding RNAs and RNA fragments with no apparent homology to parent genomes. Non-canonical transcriptions systematically transforming template DNA sequences along precise rules explain some transcripts. Among these systematic transformations, 23 systematic exchanges between nucleotides, i.e. 9 symmetric (X ↔ Y, e.g. C ↔ T) and 14 asymmetric (X → Y → Z → X, e.g. A → T → G → A) exchanges. Here, comparisons between mitochondrial swinger RNAs previously detected in a complete human transcriptome dataset (including cytosolic RNAs) and swinger RNAs detected in purified mitochondrial transcriptomic data (not including cytosolic RNAs) show high reproducibility and exclude cytosolic contaminations. These results based on next-generation sequencing Illumina technology confirm detections of mitochondrial swinger RNAs in GenBank’s EST database sequenced by the classical Sanger method, assessing the existence of swinger polymerizations

Combinatorial Fusion Rules to Describe Codon Assignment in the Standard Genetic Code

We propose combinatorial fusion rules that describe the codon assignment in the standard genetic code simply and uniformly for all canonical amino acids. These rules become obvious if the origin of the standard genetic code is considered as a result of a fusion of four protocodes: Two dominant AU and GC protocodes and two recessive AU and GC protocodes. The biochemical meaning of the fusion rules consists of retaining the complementarity between cognate codons of the small hydrophobic amino acids and large charged or polar amino acids within the protocodes. The proto tRNAs were assembled in form of two kissing hairpins with 9-base and 10-base loops in the case of dominant protocodes and two 9-base loops in the case of recessive protocodes. The fusion rules reveal the connection between the stop codons, the non-canonical amino acids, pyrrolysine and selenocysteine, and deviations in the translation of mitochondria. Using fusion rules, we predicted the existence of additional amino acids that are essential for the development of the standard genetic code. The validity of the proposed partition of the genetic code into dominant and recessive protocodes is considered referring to state-of-the-art hypotheses. The formation of two aminoacyl-tRNA synthetase classes is compatible with four-protocode partition

Relationship between mRNA secondary structure and sequence variability in Chloroplast genes: possible life history implications

<p>Abstract</p> <p>Background</p> <p>Synonymous sites are freer to vary because of redundancy in genetic code. Messenger RNA secondary structure restricts this freedom, as revealed by previous findings in mitochondrial genes that mutations at third codon position nucleotides in helices are more selected against than those in loops. This motivated us to explore the constraints imposed by mRNA secondary structure on evolutionary variability at all codon positions in general, in chloroplast systems.</p> <p>Results</p> <p>We found that the evolutionary variability and intrinsic secondary structure stability of these sequences share an inverse relationship. Simulations of most likely single nucleotide evolution in <it>Psilotum nudum </it>and <it>Nephroselmis olivacea </it>mRNAs, indicate that helix-forming propensities of mutated mRNAs are greater than those of the natural mRNAs for short sequences and vice-versa for long sequences. Moreover, helix-forming propensity estimated by the percentage of total mRNA in helices increases gradually with mRNA length, saturating beyond 1000 nucleotides. Protection levels of functionally important sites vary across plants and proteins: <it>r</it>-strategists minimize mutation costs in large genes; <it>K</it>-strategists do the opposite.</p> <p>Conclusion</p> <p>Mrna length presumably predisposes shorter mRNAs to evolve under different constraints than longer mRNAs. The positive correlation between secondary structure protection and functional importance of sites suggests that some sites might be conserved due to packing-protection constraints at the nucleic acid level in addition to protein level constraints. Consequently, nucleic acid secondary structure <it>a priori </it>biases mutations. The converse (exposure of conserved sites) apparently occurs in a smaller number of cases, indicating a different evolutionary adaptive strategy in these plants. The differences between the protection levels of functionally important sites for <it>r</it>- and <it>K-</it>strategists reflect their respective molecular adaptive strategies. These converge with increasing domestication levels of <it>K</it>-strategists, perhaps because domestication increases reproductive output.</p