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Structural Insights into tRNA Dynamics on the Ribosome
Open AccessArticle

The UGG Isoacceptor of tRNAPro Is Naturally Prone to Frameshifts

Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Faculty of Medicine, Bar-Ilan University, Henrietta Szold 8, Safed 1311502, Israel
Author to whom correspondence should be addressed.
Academic Editor: Michael Ibba
Int. J. Mol. Sci. 2015, 16(7), 14866-14883;
Received: 30 April 2015 / Revised: 23 June 2015 / Accepted: 24 June 2015 / Published: 1 July 2015
(This article belongs to the Special Issue Functions of Transfer RNAs)
Native tRNAs often contain post-transcriptional modifications to the wobble position to expand the capacity of reading the genetic code. Some of these modifications, due to the ability to confer imperfect codon-anticodon pairing at the wobble position, can induce a high propensity for tRNA to shift into alternative reading frames. An example is the native UGG isoacceptor of E. coli tRNAPro whose wobble nucleotide U34 is post-transcriptionally modified to cmo5U34 to read all four proline codons (5ʹ-CCA, 5ʹ-CCC, 5ʹ-CCG, and 5ʹ-CCU). Because the pairing of the modified anticodon to CCC codon is particularly weak relative to CCA and CCG codons, this tRNA can readily shift into both the +1 and +2-frame on the slippery mRNA sequence CCC-CG. We show that the shift to the +2-frame is more dominant, driven by the higher stability of the codon-anticodon pairing at the wobble position. Kinetic analysis suggests that both types of shifts can occur during stalling of the tRNA in a post-translocation complex or during translocation from the A to the P-site. Importantly, while the +1-frame post complex is active for peptidyl transfer, the +2-frame complex is a poor peptidyl donor. Together with our recent work, we draw a mechanistic distinction between +1 and +2-frameshifts, showing that while the +1-shifts are suppressed by the additional post-transcriptionally modified m1G37 nucleotide in the anticodon loop, the +2-shifts are suppressed by the ribosome, supporting a role of the ribosome in the overall quality control of reading-frame maintenance. View Full-Text
Keywords: +1-frameshift; +2-frameshift; cmo5U34; m1G37-tRNA; slippery mRNA sequence; ribosome; translation +1-frameshift; +2-frameshift; cmo5U34; m1G37-tRNA; slippery mRNA sequence; ribosome; translation
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Gamper, H.B.; Masuda, I.; Frenkel-Morgenstern, M.; Hou, Y.-M. The UGG Isoacceptor of tRNAPro Is Naturally Prone to Frameshifts. Int. J. Mol. Sci. 2015, 16, 14866-14883.

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