Discovery of a gene family critical to wyosine base formation in a subset of phenylalanine-specific transfer RNAs
ABSTRACT A large number of post-transcriptional base modifications in transfer RNAs have been described (Sprinzl, M., Horn, C., Brown, M., Ioudovitch, A., and Steinberg, S. (1998) Nucleic Acids Res. 26, 148-153). These modifications enhance and expand tRNA function to increase cell viability. The intermediates and genes essential for base modifications in many instances remain unclear. An example is wyebutosine (yW), a fluorescent tricyclic modification of an invariant guanosine situated on the 3'-side of the tRNA(Phe) anticodon. Although biosynthesis of yW involves several reaction steps, only a single pathway-specific enzyme has been identified (Kalhor, H. R., Penjwini, M., and Clarke, S. (2005) Biochem. Biophys. Res. Commun. 334, 433-440). We used comparative genomics analysis to identify a cluster of orthologous groups (COG0731) of wyosine family biosynthetic proteins. Gene knock-out and complementation studies in Saccharomyces cerevisiae established a role for YPL207w, a COG0731 ortholog that encodes an 810-amino acid polypeptide. Further analysis showed the accumulation of N(1)-methylguanosine (m(1)G(37)) in tRNA from cells bearing a YPL207w deletion. A similar lack of wyosine base and build-up of m(1)G(37) is seen in certain mammalian tumor cell lines. We proposed that the 810-amino acid COG0731 polypeptide participates in converting tRNA(Phe)-m(1)G(37) to tRNA(Phe)-yW.
SourceAvailable from: Hiroyuki Hori[Show abstract] [Hide abstract]
ABSTRACT: To date, more than 90 modified nucleosides have been found in tRNA and the biosynthetic pathways of the majority of tRNA modifications include a methylation step(s). Recent studies of the biosynthetic pathways have demonstrated that the availability of methyl group donors for the methylation in tRNA is important for correct and efficient protein synthesis. In this review, I focus on the methylated nucleosides and tRNA methyltransferases. The primary functions of tRNA methylations are linked to the different steps of protein synthesis, such as the stabilization of tRNA structure, reinforcement of the codon-anticodon interaction, regulation of wobble base pairing, and prevention of frameshift errors. However, beyond these basic functions, recent studies have demonstrated that tRNA methylations are also involved in the RNA quality control system and regulation of tRNA localization in the cell. In a thermophilic eubacterium, tRNA modifications and the modification enzymes form a network that responses to temperature changes. Furthermore, several modifications are involved in genetic diseases, infections, and the immune response. Moreover, structural, biochemical, and bioinformatics studies of tRNA methyltransferases have been clarifying the details of tRNA methyltransferases and have enabled these enzymes to be classified. In the final section, the evolution of modification enzymes is discussed.Frontiers in Genetics 05/2014; 5:144. DOI:10.3389/fgene.2014.00144
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ABSTRACT: RNA molecules are decorated with various chemical modifications, which are introduced post-transcriptionally by RNA-modifying enzymes. These modifications are required for proper RNA function. Among more than 100 known species of RNA modifications, several modified bases in tRNAs and rRNAs are introduced by RNA-modifying enzymes containing iron-sulfur (Fe/S) clusters. Most Fe/S-containing RNA-modifying enzymes contain radical SAM domains that catalyze a variety of chemical reactions, including methylation, methylthiolation, carboxymethylation, tricyclic purine formation, and deazaguanine formation. Lack of these modifications can cause pathological consequences. Here, we review recent studies on the biogenesis and function of RNA modifications mediated by Fe/S proteins. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases. Copyright © 2014 Elsevier B.V. All rights reserved.Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 12/2014; DOI:10.1016/j.bbamcr.2014.12.010 · 5.30 Impact Factor
Article: Radical S-Adenosylmethionine EnzymesChemical Reviews 01/2014; 114(8). DOI:10.1021/cr4004709 · 45.66 Impact Factor