A ratchet mechanism of transcription elongation and its control.
RNA chain elongation is a highly processive and accurate process that is finely regulated by numerous intrinsic and extrinsic signals. Here we describe a general mechanism that governs RNA polymerase (RNAP) movement and response to regulatory inputs such as pauses, terminators, and elongation factors. We show that E.coli RNAP moves by a complex Brownian ratchet mechanism, which acts prior to phosphodiester bond formation. The incoming substrate and the flexible F bridge domain of the catalytic center serve as two separate ratchet devices that function in concert to drive forward translocation. The adjacent G loop domain controls F bridge motion, thus keeping the proper balance between productive and inactive states of the elongation complex. This balance is critical for cell viability since it determines the rate, processivity, and fidelity of transcription.
Bar-Nahum
Gil
G
Department of Biochemistry, New York University Medical Center, New York, NY 10016, USA.
Epshtein
Vitaly
V
Ruckenstein
Andrei E
AE
Rafikov
Ruslan
R
Mustaev
Arkady
A
Nudler
Evgeny
E
D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000235:genetics; D018983:DNA Footprinting / Q000379:methods; D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics; D008962:Models, Theoretical; D009154:Mutation / Q000235:genetics; D009690:Nucleic Acid Conformation; D012265:Ribonucleotides / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D003432:Cross-Linking Reagents; D012265:Ribonucleotides; D014157:Transcription Factors; D004247:DNA; D012321:DNA-Directed RNA Polymerases