TY - JOUR
T1 - Sequence-dependent kinetic model for transcription elongation by RNA polymerase
AU - Bai, Lu
AU - Shundrovsky, Alla
AU - Wang, Michelle D.
N1 - Funding Information:
We thank Drs J. P. Sethna, J. W. Roberts, R. M. Fulbright, T. J. Santangelo, A. La Porta, K. Adelman, and S. J. Koch for stimulating scientific discussions and helpful technical advice to expedite the parameter tuning process. We thank Drs K. Adelman and T. J. Santangelo for purification of HA-tagged E. coli RNAP and the experimental transcription gel on the pKA2 template. We also thank Dr R. Landick for the pRL574 plasmid. M.D.W. was supported by grants from the NIH, the Beckman Young Investigator Award, the Alfred P. Sloan Research Fellow Award, and the Keck Foundation's Distinguished Young Scholar Award.
PY - 2004/11/19
Y1 - 2004/11/19
N2 - We present a kinetic model for the sequence-dependent motion of RNA polymerase (RNAP) during transcription elongation. For each NTP incorporation, RNAP has a net forward translocation of one base-pair along the DNA template. However, this process may involve the exploration of back-tracked and forward-tracked translocation modes. In our model, the kinetic rates for the reaction pathway, calculated based on the stabilities of the transcription elongation complex (TEC), necessarily lead to sequence-dependent NTP incorporation rates. Simulated RNAP elongation kinetics is in good agreement with data from transcription gels and single-molecule studies. The model provides a kinetic explanation for well-known back-tracked pauses at transcript positions with unstable TECs. It also predicts a new type of pause caused by an energetically unfavorable transition from pre to post-translocation modes.
AB - We present a kinetic model for the sequence-dependent motion of RNA polymerase (RNAP) during transcription elongation. For each NTP incorporation, RNAP has a net forward translocation of one base-pair along the DNA template. However, this process may involve the exploration of back-tracked and forward-tracked translocation modes. In our model, the kinetic rates for the reaction pathway, calculated based on the stabilities of the transcription elongation complex (TEC), necessarily lead to sequence-dependent NTP incorporation rates. Simulated RNAP elongation kinetics is in good agreement with data from transcription gels and single-molecule studies. The model provides a kinetic explanation for well-known back-tracked pauses at transcript positions with unstable TECs. It also predicts a new type of pause caused by an energetically unfavorable transition from pre to post-translocation modes.
UR - http://www.scopus.com/inward/record.url?scp=7444253928&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7444253928&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2004.08.107
DO - 10.1016/j.jmb.2004.08.107
M3 - Article
C2 - 15522289
AN - SCOPUS:7444253928
SN - 0022-2836
VL - 344
SP - 335
EP - 349
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 2
ER -