Frameshifting of mRNA during translation provides a strategy to expand the coding repertoire of cells and viruses. How and where in the elongation cycle +1-frameshifting occurs remains poorly understood. We describe seven ~3.5-Å-resolution cryo-EM structures of 70S ribosome complexes, allowing visualization of elongation and translocation by the GTPase elongation factor G (EF-G). Four structures with a + 1-frameshifting-prone mRNA reveal that frameshifting takes place during translocation of tRNA and mRNA. Prior to EF-G binding, the pre-translocation complex features an in-frame tRNA-mRNA pairing in the A site. In the partially translocated structure with EF-G•GDPCP, the tRNA shifts to the +1-frame near the P site, rendering the freed mRNA base to bulge between the P and E sites and to stack on the 16S rRNA nucleotide G926. The ribosome remains frameshifted in the nearly post-translocation state. Our findings demonstrate that the ribosome and EF-G cooperate to induce +1 frameshifting during tRNA-mRNA translocation.

翻译过程中 mRNA 的移码提供了扩展细胞和病毒编码库的策略。+1-移码在延伸周期中如何以及在何处发生仍然知之甚少。我们描述了 70S 核糖体复合物的七个约 3.5 Å 分辨率的冷冻电镜结构，允许通过 GTPase 延伸因子 G (EF-G) 可视化延伸和易位。四种具有 + 1 移码倾向 mRNA 的结构表明，移码发生在 tRNA 和 mRNA 易位过程中。在 EF-G 结合之前，预易位复合物在 A 位点具有框内 tRNA-mRNA 配对。在EF-G•GDPCP的部分易位结构中，tRNA转移到P位点附近的+1框，使得游离的mRNA碱基在P和E位点之间凸出并堆叠在16S rRNA核苷酸G926上。核糖体在接近易位后的状态下保持移码。我们的研究结果表明，核糖体和 EF-G 在 tRNA-mRNA 易位过程中协同诱导 +1 移码。