Structural highlights
FunctionRPOZ_ECOLI Promotes RNA polymerase assembly. Latches the N- and C-terminal regions of the beta' subunit thereby facilitating its interaction with the beta and alpha subunits.[HAMAP-Rule:MF_00366] Publication Abstract from PubMedThe 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 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. ppGpp regulates transcription elongation via direct and indirect inputs to RNA polymerase pausing and nucleotide addition.,Mueller AU, Mooney RA, Engstrom MD, Bao Y, Wolfe MB, Sah B, Buscher J, Saba J, Liu J, Darst SA, Landick R bioRxiv [Preprint]. 2026 May 14:2026.05.13.724835. doi: , 10.64898/2026.05.13.724835. PMID:42182161[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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