+Search query
-Structure paper
| Title | ppGpp regulates transcription elongation via direct and indirect inputs to RNA polymerase pausing and nucleotide addition. |
|---|---|
| Journal, issue, pages | Biorxiv, Year 2026 |
| Publish date | Mar 30, 2026 (structure data deposition date) |
Authors | Andreas U Mueller / Rachel A Mooney / Michael D Engstrom / Yu Bao / Michael B Wolfe / Balendra Sah / Jonathan Buscher / Jason Saba / James Liu / Seth A Darst / Robert Landick / ![]() |
| PubMed 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 ...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 , (p)ppGpp produced in response to charged-tRNA deficiency directly targets transcribing RNAP polymerase (RNAP) to match its pace to the pioneering ribosome on the nascent RNA (transcription-translation coupling). However, the mechanism by which (p)ppGpp slows RNAP is poorly defined. (p)ppGpp may allosterically stimulate RNAP pausing, inhibit catalysis, promote backtracking, compete for substrate GTP, inhibit GTP synthesis, or uncouple transcription-translation by inhibiting translation. Using a combination of cryo-EM, biochemical assays, and quantitative nascent elongating transcript sequencing (qNET-seq), we establish that (p)ppGpp allosterically regulates pausing and nucleotide addition via distinct motions of the RNAP swivel module and both competes with and lowers GTP in vivo. (p)ppGpp stimulates swiveling at pause sites to delay escape but may also inhibit counter-swiveling required in every round of nucleotide addition. |
External links | Biorxiv / PubMed:42182161 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.6 - 3.2 Å |
| Structure data | ![]() PDB-12eb: ![]() PDB-12ec: ![]() PDB-12ed: ![]() PDB-12ee: ![]() PDB-12ef: ![]() PDB-12eg: ![]() PDB-12eh: ![]() PDB-12ei: |
| Chemicals | ![]() ChemComp-1N7: ![]() ChemComp-MG: ![]() ChemComp-ZN: ![]() ChemComp-G4P: ![]() ChemComp-HOH: |
| Source |
|
Keywords | TRANSCRIPTION/DNA/RNA / elongation / pausing / pause escape / ppGpp / stringent response / TRANSCRIPTION / TRANSCRIPTION-DNA-RNA complex |
Movie
Controller
Structure viewers
About Yorodumi Papers



Authors

External links













Keywords