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This week we profile a recent publication in Nature from Grace Johnson (pictured, front row, second from right)
and Jean-Benoît Lalanne (back row, third from left) in the laboratory of Dr. Gene-Wei Li (back row, left) at MIT.

Can you provide a brief overview of your lab’s current research focus?

Our lab seeks to develop and utilize quantitative methods to study the central dogma in bacteria. We are generally interested in understanding how the processes of transcription, translation, and RNA decay are controlled to give rise to precise protein outputs. Further, our work aims to gain both a mechanistic and systems level understanding of the selective pressures that have shaped these highly conserved protein levels.

What is the significance of the findings in this publication?

Transcription-translation coupling, whereby the pioneering ribosome follows closely behind the transcribing RNA polymerase (RNAP), has long been considered a defining feature of the central dogma in bacteria, and establishes important regulatory mechanisms that are viewed as textbook examples of gene expression regulation. However, transcription-translation coupling has largely been characterized in E. coli and other related bacteria. In our recent work, we have demonstrated that coupling does not occur in the model gram-positive bacteria B. subtilis. Instead, in this bacterium, transcription is much faster than translation, allowing the RNAP to ‘run away’ from the ribosome. Further, we have shown that this ‘runaway transcription’ is likely not confined to B. subtilis, but rather coupled transcription and runaway transcription likely represent two distinct modes of gene expression in bacteria. Our work not only helps explain many of the divergent regulatory mechanisms observed in B. subtilis, but also reshapes our understanding of the central dogma in bacteria and underscores the importance of studying diverse bacteria.

What are the next steps for this research?

Runaway transcription has important consequences for gene expression regulation. We are interested in characterizing novel regulatory strategies that may have evolved in the context of runaway transcription. In addition, we are also interested in understanding the mechanistic underpinnings of runaway transcription that may reveal further fundamental differences between the processes of transcription and translation in E. coli and B. subtilis.

This work was funded by:

This research was supported by the NIH, the Pew Biomedical Scholars Program, a Sloan Research Fellowship, the Searle Scholars Program, the Smith Family Award for Excellence in Biomedical Research, an NSF graduate research fellowship, an NIH Pre-Doctoral Training Grant, an NSERC graduate fellowship, and an HHMI International Student Fellowship.

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