Structural insights into +1 frameshifting promoted by expanded or modification-deficient anticodon stem loops.

Tatsuya Maehigashi, Jack A Dunkle, Stacey J Miles, Christine M Dunham

Proceedings of the National Academy of Sciences of the United States of America 2014 Sep 02

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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 N1-methylguanosine at position 37 (m(1)G37) 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(1)G37 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.

Citation

Tatsuya Maehigashi, Jack A Dunkle, Stacey J Miles, Christine M Dunham. Structural insights into +1 frameshifting promoted by expanded or modification-deficient anticodon stem loops. Proceedings of the National Academy of Sciences of the United States of America. 2014 Sep 02;111(35):12740-5