It's a mod mod tRNA world.

Nature Chemical Biology (Impact Factor: 13.22). 04/2008; 4(3):162-4. DOI: 10.1038/nchembio0308-162
Source: PubMed
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    ABSTRACT: Codon usage and tRNA abundance are critical parameters for gene synthesis. However, the forces determining codon usage bias within genomes and between organisms, as well as the functional roles of biased codon compositions, remain poorly understood. Similarly, the composition and dynamics of mature tRNA populations in cells in terms of isoacceptor abundances, and the prevalence and function of base modifications are not well understood. As we begin to decipher some of the rules that govern codon usage and tRNA abundances, it is becoming clear that these parameters are a way to not only increase gene expression, but also regulate the speed of ribosomal translation, the efficiency of protein folding, and the coordinated expression of functionally related gene families. Here, we discuss the importance of codon-anticodon interactions in translation regulation and highlight the contribution of non-random codon distributions and post-transcriptional base modifications to this regulation.
    Trends in Genetics 08/2012; 28(11):574-81. DOI:10.1016/j.tig.2012.07.006 · 11.60 Impact Factor
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    ABSTRACT: Whole-genome and functional analyses suggest a wealth of secondary or auxiliary genetic information (AGI) within the redundancy component of the genetic code. Although there are multiple aspects of biased codon use, we focus on two types of auxiliary information: codon-specific translational pauses that can be used by particular proteins toward their unique folding and biased codon patterns shared by groups of functionally related mRNAs with coordinate regulation. AGI is important to genetics in general and to human disease; here, we consider influences of its three major components, biased codon use itself, variations in the tRNAome, and anticodon modifications that distinguish synonymous decoding. AGI is plastic and can be used by different species to different extents, with tissue-specificity and in stress responses. Because AGI is species-specific, it is important to consider codon-sensitive experiments when using heterologous systems; for this we focus on the tRNA anticodon loop modification enzyme, CDKAL1, and its link to type 2 diabetes. Newly uncovered tRNAome variability among humans suggests roles in penetrance and as a genetic modifier and disease modifier. Development of experimental and bioinformatics methods are needed to uncover additional means of auxiliary genetic information.
    RNA 07/2014; 20(7):977-984. DOI:10.1261/rna.044115.113 · 4.62 Impact Factor
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    ABSTRACT: tRNA genes are interspersed throughout eukaryotic DNA, contributing to genome architecture and evolution in addition to translation of the transcriptome. Codon use correlates with tRNA gene copy number in noncomplex organisms including yeasts. Synonymous codons impact translation with various outcomes, dependent on relative tRNA abundances. Availability of whole-genome sequences allowed us to examine tRNA gene copy number variation (tgCNV) and codon use in four Schizosaccharomyces species and Saccharomyces cerevisiae. tRNA gene numbers vary from 171 to 322 in the four Schizosaccharomyces despite very high similarity in other features of their genomes. In addition, we performed whole-genome sequencing of several related laboratory strains of Schizosaccharomyces pombe and found tgCNV at a cluster of tRNA genes. We examined for the first time effects of wobble rules on correlation of tRNA gene number and codon use and showed improvement for S. cerevisiae and three of the Schizosaccharomyces species. In contrast, correlation in Schizosaccharomyces japonicus is poor due to markedly divergent tRNA gene content, and much worsened by the wobble rules. In japonicus, some tRNA iso-acceptor genes are absent and others are greatly reduced relative to the other yeasts, while genes for synonymous wobble iso-acceptors are amplified, indicating wobble use not apparent in any other eukaryote. We identified a subset of japonicus-specific wobbles that improves correlation of codon use and tRNA gene content in japonicus. We conclude that tgCNV is high among Schizo species and occurs in related laboratory strains of S. pombe (and expectedly other species), and tRNAome-codon analyses can provide insight into species-specific wobble decoding.
    RNA 05/2012; 18(7):1358-72. DOI:10.1261/rna.032151.111 · 4.62 Impact Factor