NTP-driven translocation and regulation of downstream template opening by multi-subunit RNA polymerases.
Multi-subunit RNA polymerases bind nucleotide triphosphate (NTP) substrates in the pretranslocated state and carry the dNMP-NTP base pair into the active site for phosphoryl transfer. NTP-driven translocation requires that NTP substrates enter the main-enzyme channel before loading into the active site. Based on this model, a new view of fidelity and efficiency of RNA synthesis is proposed. The model predicts that, during processive elongation, NTP-driven translocation is coupled to a protein conformational change that allows pyrophosphate release: coupling the end of one bond-addition cycle to substrate loading and translocation for the next. We present a detailed model of the RNA polymerase II elongation complex based on 2 low-affinity NTP binding sites located in the main-enzyme channel. This model posits that NTP substrates, elongation factors, and the conserved Rpb2 subunit fork loop 2 cooperate to regulate opening of the downstream transcription bubble.
Burton
Zachary F
ZF
Department of Biochemistry and Molecular Biology, Michigan State University, E. Lansing, MI 48824, USA. burton@msu.edu
Feig
Michael
M
Gong
Xue Q
XQ
Zhang
Chunfen
C
Nedialkov
Yuri A
YA
Xiong
Yalin
Y
D006801:Humans; D008958:Models, Molecular; D009711:Nucleotides / Q000378:metabolism*; D011487:Protein Conformation; D021381:Protein Transport; D012319:RNA Polymerase II / Q000502:physiology*; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
D009711:Nucleotides; D035602:Transcriptional Elongation Factors; D012319:RNA Polymerase II