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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.