Transfer RNA modification: influence on translational frameshifting and metabolism

Björk, Glenn R.; Durand, Jérôme M. B.; Hagervall, Tord G.; Leipuvien≐, Ramun≐; Lundgren, Hans K.; Nilsson, K. Peter R.; Peng, Chen; Qian, Qiang; Urbonavičius, Jaunius

doi:10.1016/s0014-5793(99)00528-1

Cited by 118 publications

(119 citation statements)

References 37 publications

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“…2 Antibodies against Pus3p were prepared in rabbits by a standard immunization procedure after three injections of 0.25 mg of recombinant Pus3p per rabbit at 20-day intervals. S10 extracts from different strains (refer to legend of Fig.…”

Section: Methodsmentioning

confidence: 99%

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

Lecointe¹,

Namy²,

Hatin³

et al. 2002

Journal of Biological Chemistry

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Many different modified nucleotides are found in naturally occurring tRNA, especially in the anticodon region. Their importance for the efficiency of the translational process begins to be well documented. Here we have analyzed the in vivo effect of deleting genes coding for yeast tRNA-modifying enzymes, namely Pus1p, Pus3p, Pus4p, or Trm4p, on termination readthrough and ؉1 frameshift events. To this end, we have transformed each of the yeast deletion strains with a lacZ-luc dual-reporter vector harboring selected programmed recoding sites. We have found that only deletion of the PUS3 gene, encoding the enzyme that introduces pseudouridines at position 38 or 39 in tRNA, has an effect on the efficiency of the translation process. In this mutant, we have observed a reduced readthrough efficiency of each stop codon by natural nonsense suppressor tRNAs. This effect is solely due to the absence of pseudouridine 38 or 39 in tRNA because the inactive mutant protein Pus3[D151A]p did not restore the level of natural readthrough. Our results also show that absence of pseudouridine 39 in the slippery tRNA UAG Leu reduces ؉1 frameshift efficiency. Therefore, the presence of pseudouridine 38 or 39 in the tRNA anticodon arm enhances misreading of certain codons by natural nonsense tRNAs as well as promotes frameshifting on slippery sequences in yeast.

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Section: Methodsmentioning

confidence: 99%

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

Lecointe¹,

Namy²,

Hatin³

et al. 2002

Journal of Biological Chemistry

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“…The extensive base and backbone modifications present in natural tRNAs serve to promote translational fidelity and efficiency (Bjork et al 1999;Motorin and Helm 2010;Yi and Pan 2011). Of the more than 100 modifications identified to date, the m 1 G37 base modification is strictly conserved in evolution for tRNAs specific for leucine (CUN codons, N being one of the four natural nucleotides), proline (CCN codons), and one of the arginine isoacceptors (the CGG codon) (Bjork et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Conservation of structure and mechanism by Trm5 enzymes

Christian

Gamper

Hou

2013

RNA

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Enzymes of the Trm5 family catalyze methyl transfer from S-adenosyl methionine (AdoMet) to the N 1 of G37 to synthesize m 1 G37-tRNA as a critical determinant to prevent ribosome frameshift errors. Trm5 is specific to eukaryotes and archaea, and it is unrelated in evolution from the bacterial counterpart TrmD, which is a leading anti-bacterial target. The successful targeting of TrmD requires detailed information on Trm5 to avoid cross-species inhibition. However, most information on Trm5 is derived from studies of the archaeal enzyme Methanococcus jannaschii (MjTrm5), whereas little information is available for eukaryotic enzymes. Here we use human Trm5 (Homo sapiens; HsTrm5) as an example of eukaryotic enzymes and demonstrate that it has retained key features of catalytic properties of the archaeal MjTrm5, including the involvement of a general base to mediate one proton transfer. We also address the protease sensitivity of the human enzyme upon expression in bacteria. Using the tRNA-bound crystal structure of the archaeal enzyme as a model, we have identified a single substitution in the human enzyme that improves resistance to proteolysis. These results establish conservation in both the catalytic mechanism and overall structure of Trm5 between evolutionarily distant eukaryotic and archaeal species and validate the crystal structure of the archaeal enzyme as a useful model for studies of the human enzyme.

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“…At present, 81 different modified residues have been identified that most frequently involve the wobble position (residue 34) and the position 3 0 adjacent to the anticodon (residue 37) (Rozenski et al, 1999). All of these modifications have been shown to be essential in maintaining the correct reading frame of the translational machinery, thus improving fidelity and efficiency of protein synthesis and avoiding errors that could be detrimental for cells (Persson, 1993;Bjork et al, 1999;Urbonavicius et al, 2001). N 6 -isopentenyladenosine (i 6 A) is the only known cytokinin existing in animal tRNAs and is specifically found at position 37 of tRNA molecules that bind codons starting with uridine (Persson et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Identification and functional characterization of the candidate tumor suppressor gene TRIT1 in human lung cancer

et al. 2005

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Transfer RNA modification: influence on translational frameshifting and metabolism

Abstract: Transfer RNA modification improves the rate of aatRNA selection at the A-site and the fitness in the P-site and thereby prevents frameshifting according to a new model how frameshifting occurs [Qian et al. (1998)

Cited by 118 publications

References 37 publications

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

Lack of Pseudouridine 38/39 in the Anticodon Arm of Yeast Cytoplasmic tRNA Decreases in Vivo Recoding Efficiency

Conservation of structure and mechanism by Trm5 enzymes

Identification and functional characterization of the candidate tumor suppressor gene TRIT1 in human lung cancer

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