Article

It's a mod mod tRNA world

Nature Chemical Biology (Impact Factor: 13). 04/2008; 4(3):162-4. DOI: 10.1038/nchembio0308-162
Source: PubMed

ABSTRACT

A novel biosensor developed to visualize phosphatidylserine in intact cells suggests a new role for the anionic lipid in specifying intracellular membranes involved in signaling events.

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    • "Although tRNA abundance often reflects tRNA gene dosage, specific activity can be affected by tRNA modifications, especially to the anticodon loop. Some anticodon modifications appear to differentially affect the tRNA's activity for its exact match cognate versus wobble codon (Agris 2004Agris , 2008 Begley et al. 2007; Maraia et al. 2008 ). Increasing evidence indicates that some anticodon modification enzymes can be activated by stress, affecting dynamic control of codon-specific translation (Chan et al. 2010Chan et al. , 2012 Paredes et al. 2012; Dedon and Begley 2014). "
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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.
    Preview · Article · Jul 2014 · RNA
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    • "An advance in this area was the discovery that the wobble U34 modification enzyme Trm9 controls codon-specific decoding of functionally related mRNAs (Begley et al. 2007). These mRNAs are ''keyed'' to Trm9 because they are enriched in codons decoded by tRNA substrates of Trm9 but specifically lack synonymous codons whose tRNAs are not substrates of Trm9 (Begley et al. 2007; Maraia et al. 2008). This suggests an additional layer of information in the genetic code that can be deciphered through coordination of synonymous codon use and wobble decoding (Begley et al. 2007). "
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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.
    Preview · Article · May 2012 · RNA
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    • "tRNA gene number and arrangement are of interest to genome biologists (1–7) because tRNA abundance is matched to codon usage (3) and tRNA genes affect nuclear and genome organization [(8,9), reviewed in ref. 10, and see ref. 11]. Biased codon usage in functionally related mRNAs suggests that the relative levels of tRNA isoacceptors may reflect a means of genetic control (12–15). Most eukaryotes contain a variable number of tRNA genes, from ∼200 to several thousand (4). "
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    ABSTRACT: We used a genetic screen based on tRNA-mediated suppression (TMS) in a Schizosaccharomyces pombe La protein (Sla1p) mutant. Suppressor pre-tRNASerUCA-C47:6U with a debilitating substitution in its variable arm fails to produce tRNA in a sla1-rrm mutant deficient for RNA chaperone-like activity. The parent strain and spontaneous mutant were analyzed using Solexa sequencing. One synonymous single-nucleotide polymorphism (SNP), unrelated to the phenotype, was identified. Further sequence analyses found a duplication of the tRNASerUCA-C47:6U gene, which was shown to cause the phenotype. Ninety percent of 28 isolated mutants contain duplicated tRNASerUCA-C47:6U genes. The tRNA gene duplication led to a disproportionately large increase in tRNASerUCA-C47:6U levels in sla1-rrm but not sla1-null cells, consistent with non-specific low-affinity interactions contributing to the RNA chaperone-like activity of La, similar to other RNA chaperones. Our analysis also identified 24 SNPs between ours and S. pombe 972h- strain yFS101 that was recently sequenced using Solexa. By including mitochondrial (mt) DNA in our analysis, overall coverage increased from 52% to 96%. mtDNA from our strain and yFS101 shared 14 mtSNPs relative to a ‘reference’ mtDNA, providing the first identification of these S. pombe mtDNA discrepancies. Thus, strain-specific and spontaneous phenotypic mutations can be mapped in S. pombe by Solexa sequencing.
    Full-text · Article · Feb 2011 · Nucleic Acids Research
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