An allosteric path to transcription termination.
Transcription termination signals in bacteria occur in RNA as a strong hairpin followed by a stretch of U residues at the 3' terminus. To release the transcript, RNA polymerase (RNAP) is thought to translocate forward without RNA synthesis. Here we provide genetic and biochemical evidence supporting an alternative model in which extensive conformational changes across the enzyme lead to termination without forward translocation. In this model, flexible parts of the RNA exit channel (zipper, flap, and zinc finger) assist the initial step of hairpin folding (nucleation). The hairpin then invades the RNAP main channel, causing RNA:DNA hybrid melting, structural changes of the catalytic site, and DNA-clamp opening induced by interaction with the G(trigger)-loop. Our results envision the elongation complex as a flexible structure, not a rigid body, and establish basic principles of the termination pathway that are likely to be universal in prokaryotic and eukaryotic systems.
Epshtein
Vitaly
V
Department of Biochemistry, New York University School of Medicine, New York, NY 10016, USA.
Cardinale
Christopher J
CJ
Ruckenstein
Andrei E
AE
Borukhov
Sergei
S
Nudler
Evgeny
E
D000494:Allosteric Regulation; D001483:Base Sequence; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D008957:Models, Genetic; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D012313:RNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D012313:RNA; D012321:DNA-Directed RNA Polymerases