Structures of transcription-translation coupling complexes at each stage of the translation cycle

Bacterial transcription and translation are frequently linked through a transcribing RNA polymerase following the leading ribosome, a process termed transcription-translation coupling (TTC). Two distinct TTC structures, the collied-TTC (TTC-A) and the coupled-TTC (TTC-B), have been reported, but the biological significance of both complexes is still subject to uncertainty. Furthermore, the ribosomes in all of them are in a static state. The underlying translation dynamics within these TTCs remain elusive. Here we report cryo-EM structures of transcription-translation complexes from E.coli at various stages of the translation elongation cycle. The results show five states of TTC-B representing the whole stages of translation elongation cycle. TTC-B is compatible with ribosome conformational changes during the translation elongation and coordinates transcription elongation with translation elongation. The results show two distinct TTC-A in translational pre-translocation and translocation intermediate states in which the RNAP becomes unstable as the translation progresses. The results further show that TTC-A is the key state where the ribsomes could exert mechanical force on RNAP leading to the potential transition between TTC-A and TTC-B within mRNA spacer ranging from 7 to 9 codons and the TTC-A-dependent transcription termination within mRNA spacer shorter than 7 codons. Taken together, our results provide a comprehensive blueprint detailing the dynamic interplay of translation coupled with transcription. ### Competing Interest Statement The authors have declared no competing interest.