A novel methyltransferase required for the formation of the hypermodified nucleoside wybutosine in eucaryotic tRNA

Kalhor, Hamid Reza; Penjwini, Mahmud; Clarke, Steven

doi:10.1016/j.bbrc.2005.06.111

Cited by 35 publications

(26 citation statements)

References 28 publications

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“…It has been known for some time that the first step in Wye base formation is catalyzed by the m 1 G methyltransferase Trm5 (Droogmans and Grosjean 1987;Bjork et al 2001). Recent work has shown that subsequent biosynthesis of wybutosine involves formation of the methyl imidazole ring by Tyw1 (Waas et al 2005;Noma et al 2006), followed by addition of the a-amino-a-carboxypropyl group of methionine by Tyw2 (Kalhor et al 2005;Noma et al 2006), and methylation of guanosine N3 by Tyw3 (Noma et al 2006). Intriguingly, the last step of Wye base formation involves both methylation of the a-carboxy end group and methoxycarboxylation of the a-amino end group, with incorporation of carbon dioxide, all seemingly catalyzed by Tyw4 (Noma et al 2006;Suzuki et al 2009).…”

Section: Formation and Function Of Wybutosine Revealedmentioning

confidence: 99%

tRNA biology charges to the front

Phizicky¹,

Hopper²

2010

Genes Dev.

693

687

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tRNA biology has come of age, revealing an unprecedented level of understanding and many unexpected discoveries along the way. This review highlights new findings on the diverse pathways of tRNA maturation, and on the formation and function of a number of modifications. Topics of special focus include the regulation of tRNA biosynthesis, quality control tRNA turnover mechanisms, widespread tRNA cleavage pathways activated in response to stress and other growth conditions, emerging evidence of signaling pathways involving tRNA and cleavage fragments, and the sophisticated intracellular tRNA trafficking that occurs during and after biosynthesis.

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Section: Formation and Function Of Wybutosine Revealedmentioning

confidence: 99%

tRNA biology charges to the front

Phizicky¹,

Hopper²

2010

Genes Dev.

693

687

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“…Phenylalanine-specific tRNAs of eubacteria also lack Yb, but instead have another highly modified purine at position 37 (2-methylthio-N 6 -isopentenyladenosine). The 2-methylthio-N 6 -isopentenyladenosine modification affects anticodon structure, codon recognition, and translational efficiency in a way that is similar to Yb (6,64 7 Retention times are discussed in relation to those of A, U, G, and C. 8 Adenosine deaminase activity was verified by enzymatic assay. 9 Determined by A 254 peak integration.…”

Section: Discussionmentioning

confidence: 99%

“…(17,62,63). Mass (100 -600 m/z) and UV absorption (254, 280, 310 nm) data were collected from the eluents and, along with relative retention times, 7 were used to assign nucleoside identities according to the work of Edmonds et al (62). Absorbance and mass profiles for the tRNA Phe wt hydrolysate (Fig.…”

Section: Complementation In the Null Strain By Expression Of Ypl207w Inmentioning

confidence: 99%

Discovery of a Gene Family Critical to Wyosine Base Formation in a Subset of Phenylalanine-specific Transfer RNAs

Waas

Crécy‐Lagard

Schimmel

2005

Journal of Biological Chemistry

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In all organisms, the functions of tRNAs in translation are enhanced by a series of post-transcriptional modifications (4). Over 80 modifications are known, and their presence vastly expands the structural and chemical diversity of native tRNA (2). (In a putative RNA world, base modifications may have provided a way to diversify the chemical and structural properties of RNAs.) The modification-dependent structural stability and function correlate with increased cellular fitness and viability (5, 9). The importance of these modifications is underscored by a large investment of resources for their biosynthesis, with estimates suggesting nearly 1% of some bacterial genomes being dedicated to tRNA modification genes (4).Wyebutosine (yW) 3 of yeast phenylalanine-specific tRNA (tRNA Phe )was one of the earliest tRNA modifications to be discovered (10 -14).Wyebutosine is a fluorescent, tricyclic base and a member of the wyosine family of hypermodified guanosines. All wyosine bases (Ybs) are characterized by a 1H-imidazo[1,2-␣]purine core structure and a strict occurrence in archaeal and eukaryal tRNA Phe ( Figs. 1 and 2). Wyosine bases, isolated from different organisms, show variations in ring methylation and side chain structure (15)(16)(17)(18)(19)(20). Generally, archaeal Yb structures are less differentiated then their eukaryotic counterparts.The hydrophobic nature of yW 37 promotes stacking with adjacent bases (A 36 and A 38 ) and restricts the conformational flexibility of the anticodon (21-25). Removal of yW produced local changes in anticodon conformation, as well as long range perturbations in tRNA Phe tertiary structure (26). These structural changes were accompanied by subtle differences in codon specificity 4 and a modest increase in retroviral ribosomal frameshifting (determined in cell-free extract) (27-29). Most interesting, the tRNA Phe from mouse neuroblastoma cell lacked Yb but was more efficient than the fully modified tRNA Phe in a cell-free translation system (30 -32). Although it is unclear if hypomodified tRNAs contribute to tumor-specific properties, these tRNAs support the high levels of translation required by rapidly dividing cells. Thus, despite a good understanding of its role in maintaining anticodon structure, the function of yW in translation is unclear.Although the biosynthesis of wyebutosine has been partially characterized, the genes involved are largely unknown. Several structural components of yW were identified by metabolic labeling experiments. The purine substructure was shown as being derived from the coded guanosine (33,34). NMR studies of 13 C-enriched tRNA Phe implicated the methyl group of methionine as a source for carbon-10 (refer to Fig. 1 for numbering), and for the side chain ester and N 3 -methyl moieties (35). Conflicting evidence obscures understanding the origin of the 3-amino-3-carboxypropyl side chain (36, 37). The in vivo kinetics of Yb biosynthesis of Xenopus laevis were investigated (34). By using the sitespecifically labeled [ 32 P]tRNA Phe transcript in X. ...

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“…ScTyw2 features the typical Rossmann fold methyltransferase domain. ScTrm12 mutant tRNA was shown to contain the yW precursor 4-demethylwyosine (ImG-14 aka yW-187), the second step to yW formation, in 2005 (Kalhor et al, 2005). The trm12 deletion mutant displayed no significant difference in growth rate when compared to wild-type strains.…”

Section: Sctrm12/sctyw2mentioning

confidence: 99%

Transfer RNA Methytransferases and Their Corresponding Modifications in Budding Yeast and Humans: Activities, Predications, and Potential Roles in Human Health

Towns

Begley

2012

DNA and Cell Biology

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Throughout the kingdoms of life, transfer RNA (tRNA) undergoes over 100 enzyme-catalyzed, methyl-based modifications. Although a majority of the methylations are conserved from bacteria to mammals, the functions of a number of these modifications are unknown. Many of the proteins responsible for tRNA methylation, named tRNA methyltransferases (Trms), have been characterized in Saccharomyces cerevisiae. In contrast, only a few human Trms have been characterized. A BLAST search for human homologs of each S. cerevisiae Trm revealed a total of 34 human proteins matching our search criteria for an S. cerevisiae Trm homolog candidate. We have compiled a database cataloging basic information about each human and yeast Trm. Every S. cerevisiae Trm has at least one human homolog, while several Trms have multiple candidates. A search of cancer cell versus normal cell mRNA expression studies submitted to Oncomine found that 30 of the homolog genes display a significant change in mRNA expression levels in at least one data set. While 6 of the 34 human homolog candidates have confirmed tRNA methylation activity, the other candidates remain uncharacterized. We believe that our database will serve as a resource for investigating the role of human Trms in cellular stress signaling.

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A novel methyltransferase required for the formation of the hypermodified nucleoside wybutosine in eucaryotic tRNA

Cited by 35 publications

References 28 publications

tRNA biology charges to the front

tRNA biology charges to the front

Discovery of a Gene Family Critical to Wyosine Base Formation in a Subset of Phenylalanine-specific Transfer RNAs

Transfer RNA Methytransferases and Their Corresponding Modifications in Budding Yeast and Humans: Activities, Predications, and Potential Roles in Human Health

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