Summary information and primary citation
- PDB-id
-
12ef;
DSSR-derived features in text and
JSON formats; DNAproDB
- Class
- transcription-DNA-RNA
- Method
- cryo-EM (3.1 Å)
- Summary
- Pre-translocated RNA polymerase elemental paused
elongation complex, tl semiclosed with ppgpp (epec
semiclosed + ppgpp)
- Reference
-
Mueller AU, Mooney RA, Engstrom MD, Bao Y, Wolfe MB, Sah
B, Buscher J, Saba J, Liu J, Darst SA, Landick R (2026):
"ppGpp
regulates transcription elongation via direct and
indirect inputs to RNA polymerase pausing and nucleotide
addition." Biorxiv. doi: 10.64898/2026.05.13.724835.
- 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 <i>E. coli</i>, (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.
