Specificity mechanisms in the control of transcription.
In this overview we analyze and illustrate the principles underlying some of the specificity mechanisms that control the initiation, elongation, and termination phases of transcription. Thermodynamic mechanisms dominate in the first steps of initiation, where promoters at various levels of activation can be considered to be in competition for a limiting supply of core RNA polymerase. In the later stages of initiation, as well as in elongation and termination, the regulatory mechanisms that control specificity are largely kinetic, involving rate competition between branching reaction pathways where the outcome depends on the rates (and equilibria) of reaction and interconversion of different forms of the transcription complex. Elongation complexes are very stable at most positions along the DNA template, meaning that only RNA chain elongation (and editing) can occur at these positions. However, the stability of transcription complexes decreases abruptly when termination sequences are encountered, and here the outcome can be easily switched between elongation and termination (RNA release) by minor changes in the relative rates of these competing processes. Cis effectors, defined as sites at which regulatory proteins bind to upstream activation loci on either the DNA or the nascent RNA, play important roles in the control of both initiation and of the elongation-termination decision. Examples, drawn from studies of phage lambda N-dependent antitermination and E. coli rho-dependent termination processes, illustrate the flexibility and additivity of regulatory components within control mechanisms in transcription that involve multiple determinants. The generality of such regulatory principles are stressed.
von Hippel
P H
PH
Institute of Molecular Biology, University of Oregon, Eugene 97403, USA.
Rees
W A
WA
Rippe
K
K
Wilson
K S
KS
D000818:Animals; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D006801:Humans; D010441:Peptide Chain Elongation, Translational / Q000502:physiology; D010442:Peptide Chain Initiation, Translational / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
D012321:DNA-Directed RNA Polymerases