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Open AccessArticle

Molecular Dynamics Simulations Suggest a Non-Doublet Decoding Model of −1 Frameshifting by tRNASer3

1
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
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Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA
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Department of Cell and Molecular Biology, Uppsala University, 751 24 Uppsala, Sweden
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Department of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, Sweden
*
Authors to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 745; https://doi.org/10.3390/biom9110745
Received: 29 October 2019 / Revised: 14 November 2019 / Accepted: 14 November 2019 / Published: 18 November 2019
(This article belongs to the Special Issue Nucleic Acids, Structure and Modeling)
In-frame decoding in the ribosome occurs through canonical or wobble Watson–Crick pairing of three mRNA codon bases (a triplet) with a triplet of anticodon bases in tRNA. Departures from the triplet–triplet interaction can result in frameshifting, meaning downstream mRNA codons are then read in a different register. There are many mechanisms to induce frameshifting, and most are insufficiently understood. One previously proposed mechanism is doublet decoding, in which only codon bases 1 and 2 are read by anticodon bases 34 and 35, which would lead to −1 frameshifting. In E. coli, tRNASer3GCU can induce −1 frameshifting at alanine (GCA) codons. The logic of the doublet decoding model is that the Ala codon’s GC could pair with the tRNASer3′s GC, leaving the third anticodon residue U36 making no interactions with mRNA. Under that model, a U36C mutation would still induce −1 frameshifting, but experiments refute this. We perform all-atom simulations of wild-type tRNASer3, as well as a U36C mutant. Our simulations revealed a hydrogen bond between U36 of the anticodon and G1 of the codon. The U36C mutant cannot make this interaction, as it lacks the hydrogen-bond-donating H3. The simulation thus suggests a novel, non-doublet decoding mechanism for −1 frameshifting by tRNASer3 at Ala codons. View Full-Text
Keywords: ribosome; −1 frameshifting; S13; doublet decoding ribosome; −1 frameshifting; S13; doublet decoding
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Caulfield, T.; Coban, M.; Tek, A.; Flores, S.C. Molecular Dynamics Simulations Suggest a Non-Doublet Decoding Model of −1 Frameshifting by tRNASer3. Biomolecules 2019, 9, 745.

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