Regulation of Transcription: Transcription-Translation Coupling

Most recently we have extended our studies of transcriptional regulation to encompass transcription-translation coupling. 

In two of the three domains of life--the bacteria and the archaea--transcription and translation occur in the same cellular compartment, occur at the same time, and are coordinated processes, in which the rate of transcription by the RNA polymerase (RNAP) molecule synthesizing an mRNA is coordinated with the rate of translation by the first ribosome ("lead ribosome") translating the mRNA. 

 We recently have reported cryo-EM structures that define the structural basis of transcription‑translation coupling in the bacterium E. coli .  The results show that two bacterial transcription factors, NusG and NusA, serve as transcription-translation-coupling factors that physically bridge RNAP and the ribosome.  NusG functions as a flexible connector--a "tow chain"‑‑that potentially enables the RNAP "locomotive" to pull the ribosome "locomotive."  NusA functions as a flexible connector--a "coupling pantograph"--that potentially both enables RNAP to pull the ribosome and enables RNAP to be pushed by the ribosome.

In current work, we are determining cryo-EM structures that define the structural basis of transcription‑translation coupling by RfaH, a specialized homolog of NusG that mediates coupling transcription‑translation coupling at a subset of genes that have a specific DNA site required for RfaH to load onto RNAP.

In further current work, we are determining cryo-EM structures that explain how NusG and RfaH that define intermediates in the establishment of transcription‑translation coupling by NusG and RfaH, intermediates in the break-down of transcription‑translation coupling by NusG and RfaH, and effects of  transcription‑translation coupling by NusG and RfaH on formation and function of pause and termination hairpins.

In further current work, we are determining cryo-EM structures that define the structural basis of transcription-translation coupling in archaea, which possess a cellular RNAP that is closely related in subunit composition and structure to eukaryotic RNAP II, but that is only distantly related to bacterial RNAP.