Tight coordination between transcription and translation is crucial to maintaining the integrity of gene expression in bacteria, yet how bacteria manage to coordinate these two processes remains unclear. Possible direct physical coupling between the RNA polymerase and ribosome has been thoroughly investigated in recent years. Here, we quantitatively characterize the transcriptional kinetics of Escherichia coli under different growth conditions. Transcriptional and translational elongation remain coordinated under various nutrient conditions, as previously reported. However, transcriptional elongation was not affected under antibiotics that slowed down translational elongation. This result was also found by introducing nonsense mutation that completely dissociated transcription from translation. Our data thus provide direct evidence that translation is not required to maintain the speed of transcriptional elongation. In cases where transcription and translation are dissociated, our study provides quantitative characterization of the resulting process of premature transcriptional termination (PTT). PTT-mediated polarity caused by translation-targeting antibiotics substantially affected the coordinated expression of genes in several long operons, contributing to the key physiological effects of these antibiotics. Our results also suggest a model in which the coordination between transcriptional and translational elongation under normal growth conditions is implemented by guanosine tetraphosphate.
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The key data that support the findings of this study are summarized in the Supplementary tables. Other details are available from the corresponding author upon request.
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We are grateful to M. Kim and R. Balakrishnan for discussions. X.D. and M.Z. acknowledge the support of the National Natural Science Fund of China (grant Nos. 31700089, 31700039 and 31870028) and by CCNU (self-determined research funds of CCNU from the college’s basic research and operation of MOE, grant Nos. CCNU18QN028, CCNU18KFY01, CCNU19TS028 and CCNU18ZDPY05). M.M. and T.H. acknowledge the support of the NIH through grant No. R01GM095903.
The authors declare no competing interests.
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Zhu, M., Mori, M., Hwa, T. et al. Disruption of transcription–translation coordination in Escherichia coli leads to premature transcriptional termination. Nat Microbiol 4, 2347–2356 (2019). https://doi.org/10.1038/s41564-019-0543-1
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