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DOE OSTI · 1691525

Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon–anticodon pairing

Hoffer, Eric D.·Hong, Samuel·Sunita, S.·Maehigashi, Tatsuya·Gonzalez Jnr, Ruben L.·Whitford, Paul C.·Dunham, Christine M.
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Abstract

Modifications in the tRNA anticodon loop, adjacent to the three-nucleotide anticodon, influence translation fidelity by stabilizing the tRNA to allow for accurate reading of the mRNA genetic code. One example is the N1-methylguanosine modification at guanine nucleotide 37 (m 1 G37) located in the anticodon loop andimmediately adjacent to the anticodon nucleotides 34, 35, 36. The absence of m 1 G37 in tRNA Pro causes +1 frameshifting on polynucleotide, slippery codons. Here, we report structures of the bacterial ribosome containing tRNA Pro bound to either cognate or slippery codons to determine how the m 1 G37 modification prevents mRNA frameshifting. The structures reveal that certain codon–anticodon contexts and the lack of m 1 G37 destabilize interactions of tRNA Pro with the P site of the ribosome, causing large conformational changes typically only seen during EF-G-mediated translocation of the mRNA-tRNA pairs. These studies provide molecular insights into how m 1 G37 stabilizes the interactions of tRNA Pro with the ribosome in the context of a slippery mRNA codon.

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Hoffer, Eric D., Hong, Samuel, Sunita, S., Maehigashi, Tatsuya, Gonzalez Jnr, Ruben L., Whitford, Paul C., Dunham, Christine M.. 2020-10-05. Structural insights into mRNA reading frame regulation by tRNA modification and slippery codon–anticodon pairing. https://doi.org/10.7554/elife.51898

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