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Structural insights into +1 frameshifting promoted by expanded or modification-deficient anticodon stem loops
- Maehigashi, Tatsuya, Dunkle, Jack A., Miles, Stacey J., Dunham, Christine M.
- Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.35 pp. 12740-12745
- codons, messenger RNA, nucleotides, protein synthesis, ribosomes, transfer RNA, translation (genetics)
- Maintenance of the correct reading frame on the ribosome is essential for accurate protein synthesis. Here, we report structures of the 70S ribosome bound to frameshift suppressor tRNA Sᵘᶠᴬ⁶ and N 1-methylguanosine at position 37 (m ¹G37) modification-deficient anticodon stem loop ᴾʳᵒ, both of which cause the ribosome to decode 4 rather than 3 nucleotides, resulting in a +1 reading frame. Our results reveal that decoding at +1 suppressible codons causes suppressor tRNA Sᵘᶠᴬ⁶ to undergo a rearrangement of its 5′ stem that destabilizes U32, thereby disrupting the conserved U32–A38 base pair. Unexpectedly, the removal of the m ¹G37 modification of tRNA ᴾʳᵒ also disrupts U32–A38 pairing in a structurally analogous manner. The lack of U32–A38 pairing provides a structural correlation between the transition from canonical translation and a +1 reading of the mRNA. Our structures clarify the molecular mechanism behind suppressor tRNA-induced +1 frameshifting and advance our understanding of the role played by the ribosome in maintaining the correct translational reading frame.