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2021
Li G, Eriani G, Wang E D, Zhou X L
Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease Article de journal
Dans: Sci China Life Sci, vol. 64, no. 10, p. 1645-1660, 2021, ISBN: 33515434, (1869-1889 (Electronic) 1674-7305 (Linking) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: aminoacyl-tRNA synthetase (aaRS), central nervous system (CNS), ERIANI, Protein Biosynthesis, translation initiation, tRNA, Unité ARN
@article{,
title = {Distinct pathogenic mechanisms of various RARS1 mutations in Pelizaeus-Merzbacher-like disease},
author = {G Li and G Eriani and E D Wang and X L Zhou},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=33515434},
doi = {10.1007/s11427-020-1838-2},
isbn = {33515434},
year = {2021},
date = {2021-01-01},
urldate = {2021-01-01},
journal = {Sci China Life Sci},
volume = {64},
number = {10},
pages = {1645-1660},
abstract = {Mutations of the genes encoding aminoacyl-tRNA synthetases are highly associated with various central nervous system disorders. Recurrent mutations, including c.5A>G, p.D2G; c.1367C>T, p.S456L; c.1535G>A, p.R512Q and c.1846_1847del, p. Y616Lfs*6 of RARS1 gene, which encodes two forms of human cytoplasmic arginyl-tRNA synthetase (hArgRS), are linked to Pelizaeus-Merzbacher-like disease (PMLD) with unclear pathogenesis. Among these mutations, c.5A>G is the most extensively reported mutation, leading to a p.D2G mutation in the N-terminal extension of the long-form hArgRS. Here, we showed the detrimental effects of R512Q substitution and DeltaC mutations on the structure and function of hArgRS, while the most frequent mutation c.5A>G, p.D2G acted in a different manner without impairing hArgRS activity. The nucleotide substitution c.5A>G reduced translation of hArgRS mRNA, and an upstream open reading frame contributed to the suppressed translation of the downstream main ORF. Taken together, our results elucidated distinct pathogenic mechanisms of various RARS1 mutations in PMLD.},
note = {1869-1889 (Electronic)
1674-7305 (Linking)
Journal Article},
keywords = {aminoacyl-tRNA synthetase (aaRS), central nervous system (CNS), ERIANI, Protein Biosynthesis, translation initiation, tRNA, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Mutations of the genes encoding aminoacyl-tRNA synthetases are highly associated with various central nervous system disorders. Recurrent mutations, including c.5A>G, p.D2G; c.1367C>T, p.S456L; c.1535G>A, p.R512Q and c.1846_1847del, p. Y616Lfs*6 of RARS1 gene, which encodes two forms of human cytoplasmic arginyl-tRNA synthetase (hArgRS), are linked to Pelizaeus-Merzbacher-like disease (PMLD) with unclear pathogenesis. Among these mutations, c.5A>G is the most extensively reported mutation, leading to a p.D2G mutation in the N-terminal extension of the long-form hArgRS. Here, we showed the detrimental effects of R512Q substitution and DeltaC mutations on the structure and function of hArgRS, while the most frequent mutation c.5A>G, p.D2G acted in a different manner without impairing hArgRS activity. The nucleotide substitution c.5A>G reduced translation of hArgRS mRNA, and an upstream open reading frame contributed to the suppressed translation of the downstream main ORF. Taken together, our results elucidated distinct pathogenic mechanisms of various RARS1 mutations in PMLD.
Wijn R. De, Rollet K., G.M.Ernst F., Wellner K., Betat H., Mörl M., Sauter M.
CCA-addition in the cold: Structural characterization of the psychrophilic CCA-adding enzyme from the permafrost bacterium Planococcus halocryophilus Article de journal
Dans: Computational and Structural Biotechnology Journal, vol. 19, p. 5845-5855, 2021, ISBN: ISBN/2001-0370.
Résumé | Liens | BibTeX | Étiquettes: CCA-adding enzyme, Cold adaptation, Psychrophilic protein, Psychrophilic RNA polymerase, SAUTER, SAXS, tRNA, Unité ARN, X-ray crystallography
@article{nokey,
title = {CCA-addition in the cold: Structural characterization of the psychrophilic CCA-adding enzyme from the permafrost bacterium Planococcus halocryophilus},
author = {R. De Wijn and K. Rollet and F. G.M.Ernst and K. Wellner and H. Betat and M. Mörl and M. Sauter},
url = {https://www.sciencedirect.com/science/article/pii/S2001037021004402?via%3Dihub},
doi = {10.1016/j.csbj.2021.10.018},
isbn = {ISBN/2001-0370},
year = {2021},
date = {2021-01-01},
journal = {Computational and Structural Biotechnology Journal},
volume = {19},
pages = {5845-5855},
abstract = {CCA-adding enzymes are highly specific RNA polymerases that add and maintain the sequence C-C-A at tRNA 3ﾑ-ends. Recently, we could reveal that cold adaptation of such a polymerase is not only achieved at the expense of enzyme stability, but also at the cost of polymerization fidelity. Enzymes from psychrophilic organisms usually show an increased structural flexibility to enable catalysis at low temperatures. Here, polymerases face a dilemma, as there is a discrepancy between the need for a tightly controlled flexibility during polymerization and an increased flexibility as strategy for cold adaptation. Based on structural and biochemical analyses, we contribute to clarify the cold adaptation strategy of the psychrophilic CCA-adding enzyme from Planococcus halocryophilus, a gram-positive bacterium thriving in the arctic permafrost at low temperatures down to −15 °C. A comparison with the closely related enzyme from the thermophilic bacterium Geobacillus stearothermophilus reveals several features of cold adaptation - a significantly reduced amount of alpha-helical elements in the C-terminal tRNA-binding region and a structural adaptation in one of the highly conserved catalytic core motifs located in the N-terminal catalytic core of the enzyme},
keywords = {CCA-adding enzyme, Cold adaptation, Psychrophilic protein, Psychrophilic RNA polymerase, SAUTER, SAXS, tRNA, Unité ARN, X-ray crystallography},
pubstate = {published},
tppubtype = {article}
}
CCA-adding enzymes are highly specific RNA polymerases that add and maintain the sequence C-C-A at tRNA 3ﾑ-ends. Recently, we could reveal that cold adaptation of such a polymerase is not only achieved at the expense of enzyme stability, but also at the cost of polymerization fidelity. Enzymes from psychrophilic organisms usually show an increased structural flexibility to enable catalysis at low temperatures. Here, polymerases face a dilemma, as there is a discrepancy between the need for a tightly controlled flexibility during polymerization and an increased flexibility as strategy for cold adaptation. Based on structural and biochemical analyses, we contribute to clarify the cold adaptation strategy of the psychrophilic CCA-adding enzyme from Planococcus halocryophilus, a gram-positive bacterium thriving in the arctic permafrost at low temperatures down to −15 °C. A comparison with the closely related enzyme from the thermophilic bacterium Geobacillus stearothermophilus reveals several features of cold adaptation - a significantly reduced amount of alpha-helical elements in the C-terminal tRNA-binding region and a structural adaptation in one of the highly conserved catalytic core motifs located in the N-terminal catalytic core of the enzyme
1999
Perreau V. M., Keith G., Holmes W. M., Przykorska A., Santos M. A., Tuite M. F.
The Candida albicans CUG-decoding ser-tRNA has an atypical anticodon stem-loop structure Article de journal
Dans: J Mol Biol, vol. 293, no. 5, p. 1039-53, 1999, (0022-2836 Journal Article).
Résumé | BibTeX | Étiquettes: *Nucleic, Acid, albicans/*genetics, Anticodon/*chemistry/*genetics/metabolism, Base, Candida, cerevisiae/genetics, Code/genetics, Conformation, Evolution, Fungal/chemistry/genetics/metabolism, Genetic, Gov't, Imidazoles/metabolism, Lead/metabolism, Methylation, Methyltransferases/metabolism, Molecular, Mutation/genetics, Non-P.H.S., Non-U.S., Nucleosides/genetics/metabolism, P.H.S., Ribonucleases/metabolism, RNA, Saccharomyces, Sequence, Ser/*chemistry/*genetics/metabolism, Solutions, Support, Transfer, tRNA, U.S.
@article{,
title = {The Candida albicans CUG-decoding ser-tRNA has an atypical anticodon stem-loop structure},
author = { V. M. Perreau and G. Keith and W. M. Holmes and A. Przykorska and M. A. Santos and M. F. Tuite},
year = {1999},
date = {1999-01-01},
journal = {J Mol Biol},
volume = {293},
number = {5},
pages = {1039-53},
abstract = {In many Candida species, the leucine CUG codon is decoded by a tRNA with two unusual properties: it is a ser-tRNA and, uniquely, has guanosine at position 33 (G33). Using a combination of enzymatic (V1 RNase, RnI nuclease) and chemical (Pb(2+), imidazole) probing of the native Candida albicans ser-tRNACAG, we demonstrate that the overall tertiary structure of this tRNA resembles that of a ser-tRNA rather than a leu-tRNA, except within the anticodon arm where there is considerable disruption of the anticodon stem. Using non-modified in vitro transcripts of the C. albicans ser-tRNACAG carrying G, C, U or A at position 33, we demonstrate that it is specifically a G residue at this position that induces the atypical anticodon stem structure. Further quantitative evidence for an unusual structure in the anticodon arm of the G33-tRNA is provided by the observed change in kinetics of methylation of the G at position 37, by purified Escherichia coli m(1)G37 methyltransferase. We conclude that the anticodon arm distortion, induced by a guanosine base at position 33 in the anticodon loop of this novel tRNA, results in reduced decoding ability which has facilitated the evolution of this tRNA without extinction of the species encoding it.},
note = {0022-2836
Journal Article},
keywords = {*Nucleic, Acid, albicans/*genetics, Anticodon/*chemistry/*genetics/metabolism, Base, Candida, cerevisiae/genetics, Code/genetics, Conformation, Evolution, Fungal/chemistry/genetics/metabolism, Genetic, Gov't, Imidazoles/metabolism, Lead/metabolism, Methylation, Methyltransferases/metabolism, Molecular, Mutation/genetics, Non-P.H.S., Non-U.S., Nucleosides/genetics/metabolism, P.H.S., Ribonucleases/metabolism, RNA, Saccharomyces, Sequence, Ser/*chemistry/*genetics/metabolism, Solutions, Support, Transfer, tRNA, U.S.},
pubstate = {published},
tppubtype = {article}
}
In many Candida species, the leucine CUG codon is decoded by a tRNA with two unusual properties: it is a ser-tRNA and, uniquely, has guanosine at position 33 (G33). Using a combination of enzymatic (V1 RNase, RnI nuclease) and chemical (Pb(2+), imidazole) probing of the native Candida albicans ser-tRNACAG, we demonstrate that the overall tertiary structure of this tRNA resembles that of a ser-tRNA rather than a leu-tRNA, except within the anticodon arm where there is considerable disruption of the anticodon stem. Using non-modified in vitro transcripts of the C. albicans ser-tRNACAG carrying G, C, U or A at position 33, we demonstrate that it is specifically a G residue at this position that induces the atypical anticodon stem structure. Further quantitative evidence for an unusual structure in the anticodon arm of the G33-tRNA is provided by the observed change in kinetics of methylation of the G at position 37, by purified Escherichia coli m(1)G37 methyltransferase. We conclude that the anticodon arm distortion, induced by a guanosine base at position 33 in the anticodon loop of this novel tRNA, results in reduced decoding ability which has facilitated the evolution of this tRNA without extinction of the species encoding it.
