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Int. J. Mol. Sci. 2015, 16(7), 14866-14883;

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
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)
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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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