The UGG Isoacceptor of tRNAPro Is Naturally Prone to Frameshifts

International Journal of Molecular Sciences

Howard B. Gamper²  Isao Masuda²  Milana Frenkel-Morgenstern¹  Ya-Ming Hou² 

[1] Faculty of Medicine, Bar-Ilan University, Henrietta Szold 8, Safed 1311502, Israel; E-Mail:;Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA; E-Mails:

关键词: +1-frameshift;    +2-frameshift;    cmo⁵U34;    m¹G37-tRNA;    slippery mRNA sequence;    ribosome;    translation;   

DOI  :  10.3390/ijms160714866

来源: mdpi

【 摘 要 】

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 tRNA^Pro 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.