The machinery responsible for making proteins (e.g. ribosomal RNA, ribosomal proteins, translation factors, and tRNAs) is central to growth and development of all organisms. The regulation of the synthesis of the translation machinery in response to the nutritional state of the cell has been a central issue in the study of microbial physiology for at least fifty years. More recently, it has also become clear that an understanding of the mechanisms responsible for rRNA transcription in Escherichia coli can provide fundamental insights into understanding mechanisms of transcription in general. We are poised to address questions central to our understanding of general transcription mechanisms and to our understanding of how different regulatory systems work together. The questions addressed in the proposal are divided into four specific aims in arbitrary order. In the first aim, we will study an unanticipated role of the C-terminal domain of the alpha subunit of RNA polymerase in bacterial promoter recognition. In the second aim, we propose to determine how the rrn transcription factor Fis increases transcription from sites far upstream of the -35 element and how it affects different steps in the transcription mechanism. In the third aim, we propose to determine when different mechanisms contribute to regulation of the rrn P1 and rrn P2 promoters in response to changing nutritional conditions and how this maintains homeostasis. Also as part of this aim, we will determine the molecular interactions responsible for a key determinant in the control of rRNA transcription, the lifetime of the open complex, we will examine a new, previously unrecognized regulator of rRNA transcription, and we will begin a genomic study of tRNA promoters. In the fourth specific aim, we will use the tools of cell biology to determine the locations of rRNA operons in the bacterial nucleoid.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-MBC-2 (01))
Program Officer
Tompkins, Laurie
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
Schools of Earth Sciences/Natur
United States
Zip Code
Gourse, Richard L; Bouveret, Emmanuelle (2018) Linking glucose metabolism to the stringent response through the PTS. Proc Natl Acad Sci U S A 115:7454-7455
Chen, James; Wassarman, Karen M; Feng, Shili et al. (2017) 6S RNA Mimics B-Form DNA to Regulate Escherichia coli RNA Polymerase. Mol Cell 68:388-397.e6
Girard, Mary E; Gopalkrishnan, Saumya; Grace, Elicia D et al. (2017) DksA and ppGpp Regulate the ?S Stress Response by Activating Promoters for the Small RNA DsrA and the Anti-Adapter Protein IraP. J Bacteriol :
Cuthbert, Bonnie J; Ross, Wilma; Rohlfing, Amy E et al. (2017) Dissection of the molecular circuitry controlling virulence in Francisella tularensis. Genes Dev 31:1549-1560
Winkelman, Jared T; Vvedenskaya, Irina O; Zhang, Yuanchao et al. (2016) Multiplexed protein-DNA cross-linking: Scrunching in transcription start site selection. Science 351:1090-3
Lima, Bruno P; Lennon, Christopher W; Ross, Wilma et al. (2016) In vitro evidence that RNA Polymerase acetylation and acetyl phosphate-dependent CpxR phosphorylation affect cpxP transcription regulation. FEMS Microbiol Lett 363:fnw011
Winkelman, Jared T; Bree, Anna C; Bate, Ashley R et al. (2013) RemA is a DNA-binding protein that activates biofilm matrix gene expression in Bacillus subtilis. Mol Microbiol 88:984-97
Skolnick, Jeffrey; Zhou, Hongyi; Gao, Mu (2013) Are predicted protein structures of any value for binding site prediction and virtual ligand screening? Curr Opin Struct Biol 23:191-7
Rutherford, Steven T; Lemke, Justin J; Vrentas, Catherine E et al. (2007) Effects of DksA, GreA, and GreB on transcription initiation: insights into the mechanisms of factors that bind in the secondary channel of RNA polymerase. J Mol Biol 366:1243-57
Suthers, Patrick F; Gourse, Richard L; Yin, John (2007) Rapid responses of ribosomal RNA synthesis to nutrient shifts. Biotechnol Bioeng 97:1230-45

Showing the most recent 10 out of 85 publications