Multiple stages in codon–anticodon recognition:double-trigger mechanisms and geometric constraints☆

Ninio, Jacques

doi:10.1016/j.biochi.2006.06.002

Cited by 27 publications

(32 citation statements)

References 206 publications

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“…To discriminate effectively, the ribosome utilizes both thermodynamic and kinetic strategies to achieve this level of fidelity (Pape et al 1999;Ogle et al 2002;Gromadski and Rodnina 2004;Nierhaus 2006;Ninio 2006;Johansson et al 2008). The tRNA selection process is divided into two main phases, initial selection and proofreading, which are separated by the nearly irreversible step of GTP hydrolysis by elongation factor Tu (EF-Tu).…”

Section: Introductionmentioning

confidence: 99%

O6-Methylguanosine leads to position-dependent effects on ribosome speed and fidelity

Hudson

Zaher

2015

RNA

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Nucleic acids are under constant assault from endogenous and environmental agents that alter their physical and chemical properties. O6-methylation of guanosine (m 6 G) is particularly notable for its high mutagenicity, pairing with T, during DNA replication. Yet, while m 6 G accumulates in both DNA and RNA, little is known about its effects on RNA. Here, we investigate the effects of m 6 G on the decoding process, using a reconstituted bacterial translation system. m 6 G at the first and third position of the codon decreases the accuracy of tRNA selection. The ribosome readily incorporates near-cognate aminoacyltRNAs (aa-tRNAs) by forming m 6 G-uridine codon-anticodon pairs. Surprisingly, the introduction of m 6 G to the second position of the codon does not promote miscoding, but instead slows the observed rates of peptide-bond formation by >1000-fold for cognate aa-tRNAs without altering the rates for near-cognate aa-tRNAs. These in vitro observations were recapitulated in eukaryotic extracts and HEK293 cells. Interestingly, the analogous modification N6-methyladenosine (m 6 A) at the second position has only a minimal effect on tRNA selection, suggesting that the effects on tRNA selection seen with m 6 G are due to altered geometry of the base pair. Given that the m6G:U base pair is predicted to be nearly indistinguishable from a WatsonCrick base pair, our data suggest that the decoding center of the ribosome is extremely sensitive to changes at the second position. Our data, apart from highlighting the deleterious effects that these adducts pose to cellular fitness, shed new insight into decoding and the process by which the ribosome recognizes codon-anticodon pairs.

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Section: Introductionmentioning

confidence: 99%

O6-Methylguanosine leads to position-dependent effects on ribosome speed and fidelity

Hudson

Zaher

2015

RNA

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“…These events ensure the accuracy of translation by amplifying the destabilizing effects of mispairing in the codon-anticodon interaction (31,(42)(43)(44)(45). The selection mechanisms act at positions 1 and 2 of the codon where bases A1492, A1493, and G530 of 16S rRNA probe for the correct geometry of a W-C pairing, leaving position 3 free to accept non-W-C interactions.…”

Section: Discussionmentioning

confidence: 99%

Codon-Anticodon Recognition in the Bacillus subtilis glyQS T Box Riboswitch

Caserta¹,

Liu

Grundy

et al. 2015

Journal of Biological Chemistry

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Background:The T box riboswitch utilizes the cognate tRNA as its regulatory ligand. Results: Tolerance for mismatches at positions 1 and 3 differs from what is observed during translation. Conclusion: Regulation by the T box riboswitch utilizes codon-anticodon recognition rules that differ from those used in the ribosome. Significance: Understanding different mechanisms for RNA-RNA recognition provides insight into the constraints exerted by regulatory and translational machineries.

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“…In the second case, Viljoen and co-workers analyzed (in a mathematically correct way) some consequences of the Gromadski and Rodnina set of kinetic parameters 11 and deduced that a substantial fraction of the elongation cycle of a codon would be wasted by the ribosome having a near-cognate tRNA in its A site (see also the residence time calculation in Appendix B of Ref. 12).…”

mentioning

confidence: 98%

“…Instead, it steps back to the initial binding step, where it is fed again into the processing line. 12 This makes the procedure unnecessarily time consuming and inaccurate. In addition, due to the interdependence of the kinetic parameters, Gromadski and Rodnina had to put all the discrimination burden on forward rates, whereas most kinetic experiments merely produce ratios between forward and backward rates.…”

mentioning

confidence: 99%

Ribosomal Kinetics and Accuracy: Sequence Engineering to the Rescue

Ninio¹

2012

Journal of Molecular Biology

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Multiple stages in codon–anticodon recognition:double-trigger mechanisms and geometric constraints☆

Cited by 27 publications

References 206 publications

O6-Methylguanosine leads to position-dependent effects on ribosome speed and fidelity

O6-Methylguanosine leads to position-dependent effects on ribosome speed and fidelity

Codon-Anticodon Recognition in the Bacillus subtilis glyQS T Box Riboswitch

Ribosomal Kinetics and Accuracy: Sequence Engineering to the Rescue

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