An Isolated Class II Aminoacyl-tRNA Synthetase Insertion Domain Is Functional in Amino Acid Editing

Wong, Fai-Chu; Beuning, Penny J.; Silvers, Carmen; Musier‐Forsyth, Karin

doi:10.1074/jbc.m309627200

Cited by 87 publications

(97 citation statements)

References 50 publications

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“…The absence of an editing domain in many archaeal ThrRSs and in some bacterial ProRSs suggested that their paralogs carry out trans-editing of mischarged tRNAs. Examination of the naturally occurring paralogs AlaX, ProX, ThrX , and the ProRS paralog Ybak of Haemophilus influenzae (Wong et al 2003) showed that this is the case, as these proteins efficiently and specifically hydrolyze misacylated tRNA substrates. These data suggest that the editing domains in aaRSs may have originated from similar autonomous editing modules.…”

Section: Synthetase-like Proteinsmentioning

confidence: 99%

Aminoacyl-tRNAs: setting the limits of the genetic code

Ibba¹,

Söll²

2004

Genes Dev.

153

117

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Aminoacyl-tRNAs (aa-tRNAs) are simple molecules with a single purpose-to serve as substrates for translation. They consist of mature tRNAs to which an amino acid has been esterified at the 3Ј-end. The 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases (aaRSs, of which there are two classes), one for each amino acid of the genetic code . This would be fine if it were not for the fact that such a straightforward textbook scenario is not true in a single known living organism. aa-tRNAs lie at the heart of gene expression; they interpret the genetic code by providing the interface between nucleic acid triplets in mRNA and the corresponding amino acids in proteins. The synthesis of aa-tRNAs impacts the accuracy of translation, the expansion of the genetic code, and even provides tangible links to primary metabolism. These central roles vest immense power in aa-tRNAs, and recent studies show just how complex and diverse their synthesis is.

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Section: Synthetase-like Proteinsmentioning

confidence: 99%

Aminoacyl-tRNAs: setting the limits of the genetic code

Ibba¹,

Söll²

2004

Genes Dev.

153

117

View full text Add to dashboard Cite

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“…The function of aaRS paralogs is not restricted to amino acid biosynthesis. Truncated alanyl-, prolyl-, and threonyl-tRNA synthetase-like proteins were shown to possess esterase function and be capable of specific hydrolysis of misacylated tRNA in trans (11,12), a mechanism that should increase the fidelity of the translation process.…”

mentioning

confidence: 99%

A truncated aminoacyl–tRNA synthetase modifies RNA

Salazar

Ambrogelly

Crain

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Aminoacyl-tRNA synthetases are modular enzymes composed of a central active site domain to which additional functional domains were appended in the course of evolution. Analysis of bacterial genome sequences revealed the presence of many shorter aminoacyl-tRNA synthetase paralogs. Here we report the characterization of a well conserved glutamyl-tRNA synthetase (GluRS) paralog (YadB in Escherichia coli) that is present in the genomes of >40 species of proteobacteria, cyanobacteria, and actinobacteria. The E. coli yadB gene encodes a truncated GluRS that lacks the C-terminal third of the protein and, consequently, the anticodon binding domain. Generation of a yadB disruption showed the gene to be dispensable for E. coli growth in rich and minimal media. Unlike GluRS, the YadB protein was able to activate glutamate in presence of ATP in a tRNA-independent fashion and to transfer glutamate onto tRNA Asp . Neither tRNA Glu nor tRNA Gln were substrates. In contrast to canonical aminoacyl-tRNA, glutamate was not esterified to the 3 -terminal adenosine of tRNA Asp . Instead, it was attached to the 2-amino-5-(4,5-dihydroxy-2-cyclopenten-1-yl) moiety of queuosine, the modified nucleoside occupying the first anticodon position of tRNA Asp . Glutamyl-queuosine, like canonical Glu-tRNA, was hydrolyzed by mild alkaline treatment. Analysis of tRNA isolated under acidic conditions showed that this novel modification is present in normal E. coli tRNA; presumably it previously escaped detection as the standard conditions of tRNA isolation include an alkaline deacylation step that also causes hydrolysis of glutamyl-queuosine. Thus, this aminoacyl-tRNA synthetase fragment contributes to standard nucleotide modification of tRNA.

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“…The unique ProRS editing domain is found in at least three different structural contexts: as an insertion (INS) between motifs 2 and 3 of the aminoacylation active site of bacterial enzymes (16,25,26), as an N-terminal extension in ProRSs of lower eukaryotes (27,28), and as a free-standing editing module (25,28). A highly conserved lysine (K279 in Ec ProRS) found in most INS domain homologs is critical for posttransfer editing function (16,29).…”

mentioning

confidence: 99%

Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain

SternJohn

Hati

Siliciano

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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In contrast, the isolated INS domain displays only weak editing activity and lacks tRNA sequence specificity. These results emphasize the modular nature of synthetase editing active sites and demonstrate how in evolution, a weak editing activity can be converted to a more robust state through fusion to the body of a synthetase. In this manner, a single editing module can be distributed to different synthetases, and simultaneously acquire specificity and enhanced activity.Prolyl-tRNA synthetase ͉ Saccharomyces cerevisiae

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An Isolated Class II Aminoacyl-tRNA Synthetase Insertion Domain Is Functional in Amino Acid Editing

Cited by 87 publications

References 50 publications

Aminoacyl-tRNAs: setting the limits of the genetic code

Aminoacyl-tRNAs: setting the limits of the genetic code

A truncated aminoacyl–tRNA synthetase modifies RNA

Restoring species-specific posttransfer editing activity to a synthetase with a defunct editing domain

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