Academic literature on the topic 'Near-cognate tRNA'

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Journal articles on the topic "Near-cognate tRNA"

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Nguyen, Ha An, S. Sunita, and Christine M. Dunham. "Disruption of evolutionarily correlated tRNA elements impairs accurate decoding." Proceedings of the National Academy of Sciences 117, no. 28 (June 29, 2020): 16333–38. http://dx.doi.org/10.1073/pnas.2004170117.

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Bacterial transfer RNAs (tRNAs) contain evolutionarily conserved sequences and modifications that ensure uniform binding to the ribosome and optimal translational accuracy despite differences in their aminoacyl attachments and anticodon nucleotide sequences. In the tRNA anticodon stem−loop, the anticodon sequence is correlated with a base pair in the anticodon loop (nucleotides 32 and 38) to tune the binding of each tRNA to the decoding center in the ribosome. Disruption of this correlation renders the ribosome unable to distinguish correct from incorrect tRNAs. The molecular basis for how these two tRNA features combine to ensure accurate decoding is unclear. Here, we solved structures of the bacterial ribosome containing either wild-typetRNAGGCAlaortRNAGGCAlacontaining a reversed 32–38 pair on cognate and near-cognate codons. Structures of wild-typetRNAGGCAlabound to the ribosome reveal 23S ribosomal RNA (rRNA) nucleotide A1913 positional changes that are dependent on whether the codon−anticodon interaction is cognate or near cognate. Further, the 32–38 pair is destabilized in the context of a near-cognate codon−anticodon pair. Reversal of the pairing intRNAGGCAlaablates A1913 movement regardless of whether the interaction is cognate or near cognate. These results demonstrate that disrupting 32–38 and anticodon sequences alters interactions with the ribosome that directly contribute to misreading.
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Blanchet, Sandra, David Cornu, Isabelle Hatin, Henri Grosjean, Pierre Bertin, and Olivier Namy. "Deciphering the reading of the genetic code by near-cognate tRNA." Proceedings of the National Academy of Sciences 115, no. 12 (March 5, 2018): 3018–23. http://dx.doi.org/10.1073/pnas.1715578115.

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Some codons of the genetic code can be read not only by cognate, but also by near-cognate tRNAs. This flexibility is thought to be conferred mainly by a mismatch between the third base of the codon and the first of the anticodon (the so-called “wobble” position). However, this simplistic explanation underestimates the importance of nucleotide modifications in the decoding process. Using a system in which only near-cognate tRNAs can decode a specific codon, we investigated the role of six modifications of the anticodon, or adjacent nucleotides, of the tRNAs specific for Tyr, Gln, Lys, Trp, Cys, and Arg inSaccharomyces cerevisiae.Modifications almost systematically rendered these tRNAs able to act as near-cognate tRNAs at stop codons, even though they involve noncanonical base pairs, without markedly affecting their ability to decode cognate or near-cognate sense codons. These findings reveal an important effect of modifications to tRNA decoding with implications for understanding the flexibility of the genetic code.
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Vimaladithan, A., and P. J. Farabaugh. "Special peptidyl-tRNA molecules can promote translational frameshifting without slippage." Molecular and Cellular Biology 14, no. 12 (December 1994): 8107–16. http://dx.doi.org/10.1128/mcb.14.12.8107.

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Recently we described an unusual programmed +1 frameshift event in yeast retrotransposon Ty3. Frameshifting depends on the presence of peptidyl-tRNA(AlaCGC) on the GCG codon in the ribosomal P site and on a translational pause stimulated by the slowly decoded AGU codon. Frameshifting occurs on the sequence GCG-AGU-U by out-of-frame binding of a valyl-tRNA to GUU without slippage of peptidyl-tRNA(AlaCGC). This mechanism challenges the conventional understanding that frameshift efficiency must correlate with the ability of mRNA-bound tRNA to slip between cognate or near-cognate codons. Though frameshifting does not require slippery tRNAs, it does require special peptidyl-tRNAs. We show that overproducing a second isoacceptor whose anticodon had been changed to CGC eliminated frameshifting; peptidyl-tRNA(AlaCGC) must have a special capacity to induce +1 frameshifting in the adjacent ribosomal A site. In order to identify other special peptidyl-tRNAs, we tested the ability of each of the other 63 codons to replace GCG in the P site. We found no correlation between the ability to stimulate +1 frameshifting and the ability of the cognate tRNA to slip on the mRNA--several codons predicted to slip efficiently do not stimulate frameshifting, while several predicted not to slip do stimulate frameshifting. By inducing a severe translational pause, we identified eight tRNAs capable of inducing measurable +1 frameshifting, only four of which are predicted to slip on the mRNA. We conclude that in Saccharomyces cerevisiae, special peptidyl-tRNAs can induce frameshifting dependent on some characteristic(s) other than the ability to slip on the mRNA.
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Vimaladithan, A., and P. J. Farabaugh. "Special peptidyl-tRNA molecules can promote translational frameshifting without slippage." Molecular and Cellular Biology 14, no. 12 (December 1994): 8107–16. http://dx.doi.org/10.1128/mcb.14.12.8107-8116.1994.

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Recently we described an unusual programmed +1 frameshift event in yeast retrotransposon Ty3. Frameshifting depends on the presence of peptidyl-tRNA(AlaCGC) on the GCG codon in the ribosomal P site and on a translational pause stimulated by the slowly decoded AGU codon. Frameshifting occurs on the sequence GCG-AGU-U by out-of-frame binding of a valyl-tRNA to GUU without slippage of peptidyl-tRNA(AlaCGC). This mechanism challenges the conventional understanding that frameshift efficiency must correlate with the ability of mRNA-bound tRNA to slip between cognate or near-cognate codons. Though frameshifting does not require slippery tRNAs, it does require special peptidyl-tRNAs. We show that overproducing a second isoacceptor whose anticodon had been changed to CGC eliminated frameshifting; peptidyl-tRNA(AlaCGC) must have a special capacity to induce +1 frameshifting in the adjacent ribosomal A site. In order to identify other special peptidyl-tRNAs, we tested the ability of each of the other 63 codons to replace GCG in the P site. We found no correlation between the ability to stimulate +1 frameshifting and the ability of the cognate tRNA to slip on the mRNA--several codons predicted to slip efficiently do not stimulate frameshifting, while several predicted not to slip do stimulate frameshifting. By inducing a severe translational pause, we identified eight tRNAs capable of inducing measurable +1 frameshifting, only four of which are predicted to slip on the mRNA. We conclude that in Saccharomyces cerevisiae, special peptidyl-tRNAs can induce frameshifting dependent on some characteristic(s) other than the ability to slip on the mRNA.
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Ieong, Ka-Weng, Gabriele Indrisiunaite, Arjun Prabhakar, Joseph D. Puglisi, and Måns Ehrenberg. "N 6-Methyladenosines in mRNAs reduce the accuracy of codon reading by transfer RNAs and peptide release factors." Nucleic Acids Research 49, no. 5 (February 9, 2021): 2684–99. http://dx.doi.org/10.1093/nar/gkab033.

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Abstract We used quench flow to study how N6-methylated adenosines (m6A) affect the accuracy ratio between kcat/Km (i.e. association rate constant (ka) times probability (Pp) of product formation after enzyme-substrate complex formation) for cognate and near-cognate substrate for mRNA reading by tRNAs and peptide release factors 1 and 2 (RFs) during translation with purified Escherichia coli components. We estimated kcat/Km for Glu-tRNAGlu, EF-Tu and GTP forming ternary complex (T3) reading cognate (GAA and Gm6AA) or near-cognate (GAU and Gm6AU) codons. ka decreased 10-fold by m6A introduction in cognate and near-cognate cases alike, while Pp for peptidyl transfer remained unaltered in cognate but increased 10-fold in near-cognate case leading to 10-fold amino acid substitution error increase. We estimated kcat/Km for ester bond hydrolysis of P-site bound peptidyl-tRNA by RF2 reading cognate (UAA and Um6AA) and near-cognate (UAG and Um6AG) stop codons to decrease 6-fold or 3-fold by m6A introduction, respectively. This 6-fold effect on UAA reading was also observed in a single-molecule termination assay. Thus, m6A reduces both sense and stop codon reading accuracy by decreasing cognate significantly more than near-cognate kcat/Km, in contrast to most error inducing agents and mutations, which increase near-cognate at unaltered cognate kcat/Km.
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O’Connor, Michael. "tRNA imbalance promotes −1 frameshifting via near-cognate decoding." Journal of Molecular Biology 279, no. 4 (June 1998): 727–36. http://dx.doi.org/10.1006/jmbi.1998.1832.

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Wohlgemuth, Ingo, Corinna Pohl, Joerg Mittelstaet, Andrey L. Konevega, and Marina V. Rodnina. "Evolutionary optimization of speed and accuracy of decoding on the ribosome." Philosophical Transactions of the Royal Society B: Biological Sciences 366, no. 1580 (October 27, 2011): 2979–86. http://dx.doi.org/10.1098/rstb.2011.0138.

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Speed and accuracy of protein synthesis are fundamental parameters for the fitness of living cells, the quality control of translation, and the evolution of ribosomes. The ribosome developed complex mechanisms that allow for a uniform recognition and selection of any cognate aminoacyl-tRNA (aa-tRNA) and discrimination against any near-cognate aa-tRNA, regardless of the nature or position of the mismatch. This review describes the principles of the selection—kinetic partitioning and induced fit—and discusses the relationship between speed and accuracy of decoding, with a focus on bacterial translation. The translational machinery apparently has evolved towards high speed of translation at the cost of fidelity.
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Pernod, Ketty, Laure Schaeffer, Johana Chicher, Eveline Hok, Christian Rick, Renaud Geslain, Gilbert Eriani, Eric Westhof, Michael Ryckelynck, and Franck Martin. "The nature of the purine at position 34 in tRNAs of 4-codon boxes is correlated with nucleotides at positions 32 and 38 to maintain decoding fidelity." Nucleic Acids Research 48, no. 11 (April 8, 2020): 6170–83. http://dx.doi.org/10.1093/nar/gkaa221.

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Abstract Translation fidelity relies essentially on the ability of ribosomes to accurately recognize triplet interactions between codons on mRNAs and anticodons of tRNAs. To determine the codon-anticodon pairs that are efficiently accepted by the eukaryotic ribosome, we took advantage of the IRES from the intergenic region (IGR) of the Cricket Paralysis Virus. It contains an essential pseudoknot PKI that structurally and functionally mimics a codon-anticodon helix. We screened the entire set of 4096 possible combinations using ultrahigh-throughput screenings combining coupled transcription/translation and droplet-based microfluidics. Only 97 combinations are efficiently accepted and accommodated for translocation and further elongation: 38 combinations involve cognate recognition with Watson-Crick pairs and 59 involve near-cognate recognition pairs with at least one mismatch. More than half of the near-cognate combinations (36/59) contain a G at the first position of the anticodon (numbered 34 of tRNA). G34-containing tRNAs decoding 4-codon boxes are almost absent from eukaryotic genomes in contrast to bacterial genomes. We reconstructed these missing tRNAs and could demonstrate that these tRNAs are toxic to cells due to their miscoding capacity in eukaryotic translation systems. We also show that the nature of the purine at position 34 is correlated with the nucleotides present at 32 and 38.
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Mittelstaet, Joerg, Andrey L. Konevega, and Marina V. Rodnina. "Distortion of tRNA upon Near-cognate Codon Recognition on the Ribosome." Journal of Biological Chemistry 286, no. 10 (January 6, 2011): 8158–64. http://dx.doi.org/10.1074/jbc.m110.210021.

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Roy, Bijoyita, Westley J. Friesen, Yuki Tomizawa, John D. Leszyk, Jin Zhuo, Briana Johnson, Jumana Dakka, et al. "Ataluren stimulates ribosomal selection of near-cognate tRNAs to promote nonsense suppression." Proceedings of the National Academy of Sciences 113, no. 44 (October 4, 2016): 12508–13. http://dx.doi.org/10.1073/pnas.1605336113.

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A premature termination codon (PTC) in the ORF of an mRNA generally leads to production of a truncated polypeptide, accelerated degradation of the mRNA, and depression of overall mRNA expression. Accordingly, nonsense mutations cause some of the most severe forms of inherited disorders. The small-molecule drug ataluren promotes therapeutic nonsense suppression and has been thought to mediate the insertion of near-cognate tRNAs at PTCs. However, direct evidence for this activity has been lacking. Here, we expressed multiple nonsense mutation reporters in human cells and yeast and identified the amino acids inserted when a PTC occupies the ribosomal A site in control, ataluren-treated, and aminoglycoside-treated cells. We find that ataluren’s likely target is the ribosome and that it produces full-length protein by promoting insertion of near-cognate tRNAs at the site of the nonsense codon without apparent effects on transcription, mRNA processing, mRNA stability, or protein stability. The resulting readthrough proteins retain function and contain amino acid replacements similar to those derived from endogenous readthrough, namely Gln, Lys, or Tyr at UAA or UAG PTCs and Trp, Arg, or Cys at UGA PTCs. These insertion biases arise primarily from mRNA:tRNA mispairing at codon positions 1 and 3 and reflect, in part, the preferred use of certain nonstandard base pairs, e.g., U-G. Ataluren’s retention of similar specificity of near-cognate tRNA insertion as occurs endogenously has important implications for its general use in therapeutic nonsense suppression.
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Dissertations / Theses on the topic "Near-cognate tRNA"

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Kučerová, Michaela. "Cysteinová tRNA reguluje proteosyntézu v lidských buněčných liniích." Master's thesis, 2021. http://www.nusl.cz/ntk/nusl-445948.

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A significant number of known human genetic diseases is associated with nonsense mutations leading to the introduction of a premature termination codon into the coding sequence. A termination codon can be read through by its near-cognate tRNA (tRNA with two anticodon nucleotides base-pairing with a stop codon); potentially generating C-terminally extended protein variants. In yeast, UGA stop codon was described to be read through by tRNA-Trp and tRNA-Cys. Similar was observed for tRNA-Trp in human HEK293T cell line. The aim of this thesis was to investigate if human tRNA-Cys can act as a near-cognate tRNA in human HEK293T cell line. There are two isoacceptors which constitute the tRNA-Cys family, with ACA and GCA anticodon. There are 1 and 23 isodecoders to the ACA and GCA anticodons, respectively. Here, altogether as many as nine tRNA-Cys isodecoders (distinct in their sequence and with varying levels of expression) were tested for their ability to increase UGA readthrough in HEK293T using p2luci and pSGDluc dual-luciferase reporter vectors. In both p2luci and pSGDluc, we observed that at least one tRNA-Cys isodecoder, tRNA-Cys-GCA-4-1, is capable of significantly elevating the UGA readthrough levels when overexpressed in HEK293T. This indicates that similarly to yeast, tRNA-Cys is capable of...
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