Peer-Reviewed Publication
bioRxiv2026May 14, 2026Journal Article
ppGpp regulates transcription elongation via direct and indirect inputs to RNA polymerase pausing and nucleotide addition.
Andreas U Mueller1,2, Rachel A Mooney3,2, Michael D Engstrom3,2,4, Yu Bao3,5, Michael B Wolfe3,6, Balendra Sah3, Jonathan Buscher3, Jason Saba3,7, James Liu3,8, Seth A Darst1, Robert Landick3,9,2
1Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065, USA.
2These authors contributed equally.
3Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
4Present address: Cardio Diagnostics, Inc., Iowa City, IA 52245, USA.
5Present address: Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
6Present address: Information Technology Services, Florida State University, Tallahassee, FL 32306, USA.
7Present address: AbbVie, Madison Peptide Therapeutics, 603 Science Drive, Madison, WI 53711, USA.
8Present address: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
9Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
Abstract
The signaling molecules guanosine 5'-tri/diphosphate 3'-diphosphate, (p)ppGpp, control bacterial protein synthesis rates and cell growth by targeting transcription, translation, NTP synthesis, and other functions. In lineages like E. coli, (p)ppGpp produced in response to charged-tRNA deficiency directly targets transcribing RNAP polymerase (RNAP) to match its pace to the pioneering ribosome on th…
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