Document Type
Article
Publication Date
1-12-2021
Abstract
While genome recoding using quadruplet codons to incorporate non-proteinogenic amino acids is attractive for biotechnology and bioengineering purposes, the mechanism through which such codons are translated is poorly understood. Here we investigate translation of quadruplet codons by a +1-frameshifting tRNA, SufB2, that contains an extra nucleotide in its anticodon loop. Natural post-transcriptional modification of SufB2 in cells prevents it from frameshifting using a quadruplet-pairing mechanism such that it preferentially employs a triplet-slippage mechanism. We show that SufB2 uses triplet anticodon-codon pairing in the 0-frame to initially decode the quadruplet codon, but subsequently shifts to the +1-frame during tRNA-mRNA translocation. SufB2 frameshifting involves perturbation of an essential ribosome conformational change that facilitates tRNA-mRNA movements at a late stage of the translocation reaction. Our results provide a molecular mechanism for SufB2-induced +1 frameshifting and suggest that engineering of a specific ribosome conformational change can improve the efficiency of genome recoding.
Recommended Citation
Gamper, Howard; Li, Haixing; Masuda, Isao; Miklos Robkis, D.; Christian, Thomas; Conn, Adam B.; Blaha, Gregor; Petersson, E. James; Gonzalez, Ruben L.; and Hou, Ya-Ming, "Insights into genome recoding from the mechanism of a classic +1-frameshifting tRNA." (2021). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 177.
https://jdc.jefferson.edu/bmpfp/177
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
33436566
Language
English
Comments
This article is the author’s final published version in Nature Communications, Volume 12, Issue 1, January 2021, Article number 328.
The published version is available at https://doi.org/10.1038/s41467-020-20373-z. Copyright © Gamper et al.