DnaA-dependent riboswitch for transcription attenuation

Transcription attenuation has been believed to be controlled by alternative configurations of RNA secondary structures through arresting or releasing the ribosome on the leader RNA molecule in response to limitation or sufficiency of specific amino acid. Here we report the first example of a DnaA-dependent riboswitch for transcription attenuation. We establish that transcription attenuation of the Escherichia coli his operon is regulated by DnaA-dependent alternative configurations of mRNA secondary structures. We show that (i) transcription attenuation of the his operon depends on both DnaA and the HisL-SL RNA; (ii) DnaA binds to rDnaA-boxes of the HisL-SL RNA and subsequently attenuates transcription of the operon; disruptions in these rDnaA-boxes affect both binding affinity for DnaA and subsequent attenuation; (iii) rDnaA-boxes of the HisL-SL RNA are phylogenetically conserved in gram-negative bacteria; (iv) tRNAHis strengthens the attenuation of the his operon, dependent on the presence of both HisL-SL RNA and DnaA; (v) the HisL-SL RNA-mediated control for the his operon is evolutionarily important. We show that a DnaA-dependent riboswitch regulates the his operon attenuation by alternative secondary structures of the HisL-SL RNA depending on binding of DnaA to rDnaA-boxes with assistance of tRNAHis.