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Molecular Dynamics Simulations Suggest a Non-Doublet Decoding Model of -1 Frameshifting by tRNA(Ser3)
Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.ORCID iD: 0000-0002-1055-3069
Mayo Clin, Dept Canc Biol, Jacksonville, FL 32224 USA.ORCID iD: 0000-0001-6396-6759
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Stockholm Univ, Dept Biochem & Biophys, S-10691 Stockholm, Sweden.
2019 (English)In: Biomolecules, E-ISSN 2218-273X, Vol. 9, no 11, article id 745Article in journal (Refereed) Published
Abstract [en]

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, tRNA(GCU)(Ser3) 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 tRNA(Ser3 ')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 tRNA(Ser3), 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 tRNA(Ser3) at Ala codons.

Place, publisher, year, edition, pages
2019. Vol. 9, no 11, article id 745
Keywords [en]
ribosome, -1 frameshifting, S13, doublet decoding
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-400758DOI: 10.3390/biom9110745ISI: 000502267900106PubMedID: 31752208OAI: oai:DiVA.org:uu-400758DiVA, id: diva2:1382491
Funder
Swedish Research Council, VR-M 2016-06301Available from: 2020-01-03 Created: 2020-01-03 Last updated: 2020-01-03Bibliographically approved

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