Hostname: page-component-7479d7b7d-pfhbr Total loading time: 0 Render date: 2024-07-10T16:29:57.695Z Has data issue: false hasContentIssue false
  • English
  • Français

The Influence of Look-Ahead on the Error Rate of Transcription

Published online by Cambridge University Press:  28 April 2010

Y. R. Yamada  and
C. S. Peskin
Y. R. Yamada*
Affiliation:
Department of Mathematics, University of Michigan, 48109-1043 Ann Arbor, MI, USA
C. S. Peskin
Affiliation:
Courant Institute of Mathematical Sciences, New York University, New York, NY, USA
*
1 Corresponding author. E-mail: yryamada@umich.edu
Get access

Abstract

In this paper we study the error rate of RNA synthesis in the look-ahead model for the random walk of RNA polymerase along DNA during transcription. The model’s central assumption is the existence of a window of activity in which ribonucleoside triphosphates (rNTPs) bind reversibly to the template DNA strand before being hydrolyzed and linked covalently to the nascent RNA chain. An unknown, but important, integer parameter of this model is the window size w. Here, we use mathematical analysis and computer simulation to study the rate at which transcriptional errors occur as a function of w. We find dramatic reduction in the error rate of transcription as w increases, especially for small values of w. The error reduction method provided by look-ahead occurs before hydrolysis and covalent linkage of rNTP to the nascent RNA chain, and is therefore distinct from error correction mechanisms that have previously been considered.

Keywords

transcription modelingelongation dynamics of transcriptionerror-correcting mechanismsGillespie simulationchemical master equation
Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 5 , Issue 3: Mathematical modeling in the medical sciences , 2010 , pp. 206 - 227
Copyright
© EDP Sciences, 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

A. Alon. An introduction to systems biology: design principles of biological circuits. Chapman and Hall, Boca Raton, 2007.
Abbodanzieri, E., Greenleaf, W., Shaevitz, J., Landick, R., Block, S.. Direct observation of base-pair stepping by RNA polymerase . Nature, 438 (2005), 460-465.CrossRefGoogle Scholar
Bai, L., Fulbright, R., Wang, M.. Mechanochemical kinetics of transcription elongation . Phys. Rev. Lett., 98 (2007), No. 6, 068103.CrossRefGoogle ScholarPubMed
Bar-Nahum, G., Epshtein, V., Ruckenstein, A., Rafikov, R., Mustaev, A., Nudler, E.. A ratchet mechanism of transcription elongation and its control . Cell, 120 (2005), No. 2, 183-193.CrossRefGoogle ScholarPubMed
Blank, A., Gallant, J., Burgess, R., Loeb, L.. An RNA polymerase mutant with reduced accuracy of chain elongation . Biochemistry, 25 (1986), No. 20, 5920-5928.CrossRefGoogle ScholarPubMed
Chen, Y., Chafin, D., Price, D., Greenleaf, A.. Drosophila RNA polymerase II mutants that affect transcription elongation . Jour. Biol. Chem., 271 (1996), No. 11, 5993-5999.CrossRefGoogle ScholarPubMed
Eichhorn, G., Chuknyisky, P., Butzow, J., Beal, R., Garland, C., Janzen, C., Clark, P., Tarien, E.. A structural model for fidelity in transcription . Proc. Natl. Acad. Sci., 91 (1994), No. 16, 7613-7617.CrossRefGoogle ScholarPubMed
Gillespie, D.. A general method for numerically simulating the stochastic time evolution of coupled chemical reactions . J. Comp. Phys., 22 (1976), No. 4, 403-434.CrossRefGoogle Scholar
Gillespie, D.. Exact stochastic simulation of coupled chemical reactions . J. Phys. Chem., 81 (1977), No. 25, 2340-2361.CrossRefGoogle Scholar
Greive, S., von Hippel, P.. Thinking quantitatively about transcriptional regulation . Nat. Rev. Mol. Cell Biol., 6 (2005), 221-232.CrossRefGoogle ScholarPubMed
Herbert, K., Greenleaf, W., Block, S.. Single-molecule studies of RNA polymerase: motoring along . Annu. Rev. Biochem., 77 (2008), 149-176.CrossRefGoogle ScholarPubMed
Hlavacek, W., Redondo, A., Metzger, H., Wofsy, C., Goldstein, B.. Kinetic proofreading models for cell signaling predict ways to escape kinetic proofreading . Proc. Natl. Acad. Sci., 98 (2001), No. 13, 7295-7300.CrossRefGoogle ScholarPubMed
Holmes, S., Santangelo, T., Cunningham, C., Roberts, J., Erie, D.. Kinetic investigation of Escherichia coli RNA polymerase mutants that influence nucleotide discrimination and transcription fidelity . Jour. Biol. Chem., 281(2006), No. 27, 18677-18683. CrossRefGoogle ScholarPubMed
Hopfield, J.. Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity . Proc. Natl. Acad. Sci., 71 (1974), No. 10, 4135-4139.CrossRefGoogle ScholarPubMed
Howe, K., Kane, C., Ares, A.. Perturbation of transcription elongation influences the fidelity of internal exon inclusion in saccharomyces cerevisiae . RNA, 9 (2003), No. 8, 993-1006.CrossRefGoogle ScholarPubMed
Jeon, C., Agarwal, K.. Fidelity of RNA polymerase II transcription controlled by elongation factor TFIIS . Proc. Natl. Acad. Sci., 93 (1996), No. 24, 13677-13682.CrossRefGoogle ScholarPubMed
Kireeva, M., Nedlialkov, Y., Cremona, G., Purtov, Y., Lubkowska, L., Malagon, F., Burton, Z., Strathern, J., Kashlev, M.. Transient reversal of RNA polymerase II active site closing controls fidelity of transcription elongation . Mol. Cell, 30 (2008), No. 5, 557-566.CrossRefGoogle ScholarPubMed
Libby, R., Gallant, J.. The role of RNA polymerase in transcriptional fidelity . Mol. Microbiol., 5 (1991), No. 5, 999-1004.CrossRefGoogle ScholarPubMed
Libby, R., Gallant, J. Phosphorolytic error correction during transcription . Mol. Microbiol., 12 (1994), No. 1, 121-129.CrossRefGoogle ScholarPubMed
Libby, R., Nelson, L., Calvo, J., Gallant, J.. Transcriptional proofreading in escherichia coli . EMBO Jour., 8 (1989), No. 10, 3153-3158.Google ScholarPubMed
Malagon, F., Kireeva, M., Shafer, B., Lubkowska, L., Kashlev, M., Strathern, J.. Mutations in the saccharomyces cerevisiae RPB1 gene conferring hypersensitivity to 6-Azauracil . Genetics, 172 (2006), No. 4, 2201-2209.CrossRefGoogle ScholarPubMed
Mason, P., Struhl, K.. Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo . Mol. Cell, 17 (2005), No. 6, 831-840.CrossRefGoogle ScholarPubMed
de la Mata, M., Alonso, C., Kadener, S., Fededa, J., Blaustein, M., Pelisch, J., Cramer, P., Bentley, D., Kornblihtt, A.. A Slow RNA Polymerase II Affects Alternative Splicing in Vivo . Mol. Cell, 12 (2003), No. 2, 525-532.CrossRefGoogle ScholarPubMed
McKeithan, T.. Kinetic proofreading in T-cell receptor signal transduction . Proc. Natl. Acad. Sci., 92 (1995), No. 11, 5042-5046.CrossRefGoogle ScholarPubMed
Ninio, J.. Kinetic amplification of enzyme discrimination . Biochimie, 57 (1975), No. 5, 587-595.CrossRefGoogle ScholarPubMed
Roberts, J., Shankar, S., Filter, J.. RNA polymerase elongation Ffactors . Annu. Rev. Microbiol., 62 (2008), 211-233.CrossRefGoogle Scholar
Roussel, J., Zhu, R.. Stochastic kinetics description of a simple transcription model . Bull. Math. Biol., 68 (2006), No. 7, 1681-1713.CrossRefGoogle ScholarPubMed
Shaevitz, J., Abbondanzieri, E., Landick, R., Block , S.. Backtracking by single RNA polymerase molecules observed at near-base-pair resolution . Nature, 426 (2003), 684-687.CrossRefGoogle ScholarPubMed
Sims, R., Belotserkovskaya, R., Reinberg, D.. Elongation by RNA polymerase II: the short and long of it . Genes Dev., 18 (2004), 2437-2468.CrossRefGoogle Scholar
Springgate, C., Loeb, L.. On the fidelity of transcription by escherichia coli ribonucleic acid polymerase . J. Mol. Biol., 97 (1975), No. 4, 577-591.CrossRefGoogle ScholarPubMed
Stepanova, E., Lee, J., Ozerova, M., Semenova, E., Datsenko, K., Wanner, B., Severinov, K., Borukhov, S.. Analysis of promoter targets for Escheichia coli transcription elongation factor GreA in vivo and in vitro . J. Bateriol., 189 (2007), No. 24, 8772-8785.CrossRefGoogle Scholar
Swain, P., Siggia, E.. The role of proofreading in signal transduction specifity . Biophys. J., 82 (2007), No. 6, 2928-2933.CrossRefGoogle Scholar
Tadigotla, V., O’Maoileidigh, D., Sengupta, A., Epshtein, V., Ebright, R., Nudler, E., Ruckenstein, A.. Thermodynamic and kinetic modeling of transcriptional pausing . Prof. Natl. Acad. Sci.,103 (2006), No. 12, 4439-4444. CrossRefGoogle ScholarPubMed
Thomas, J., Platas, A., Hawley, D.. Transcriptional fidelity and proofreading by RNA polymerase II Cell, 93 (1998), No. 4, 627-637. CrossRefGoogle ScholarPubMed
Tlusty, T., Bar-Ziv, R., Libchaber, A.. High-fidelity DNA sensing by protein binding fluctuations . Phys. Rev. Lett., 93 (2004), No. 25, 2581031.CrossRefGoogle ScholarPubMed
Vogel, U., Jensen, K.. The RNA chain elongation rate in escherichia coli depends on the growth rate . J. Bacteriol., 176 (1994), No. 10, 2807-2813.CrossRefGoogle ScholarPubMed
Voliotis, M., Cohen, N., Molina-Paris, C., Liverpool, T.. Fluctuations, pauses, and backtracking in DNA transcription . Biophys. J., 94 (2008), No. 2, 334-348.CrossRefGoogle ScholarPubMed
M. Voliotis, N. Cohen, C. Molina-Paris, T. Liverpool. Backtracking and error correction in DNA transcription in The Art and Science of Statistical Bioinformatics. 104-107, Leeds University Press, Leeds, 2008.
Xie, P.. A dynamic model for transcription elongation and sequence-dependent short pauses by RNA polymerase . BioSystems, 93 (2008), 199-210.CrossRefGoogle ScholarPubMed
Y. Yamada, C. Peskin. A chemical kinetic model of transcriptional elongation. LANL ArXiv (2006), q-bio.BM/0603012.
Yamada, Y., Peskin, C.. A look-ahead model for the elongation dynamics of transcription . Biophys. J., 96 (2009), No. 8, 3015-3031.CrossRefGoogle Scholar
Zenkin, N., Yuzenkova, Y., Severinov, K.. Transcript-assisted transcriptional proofreading . Science, 313 (2006), No. 5786, 518-520.CrossRefGoogle ScholarPubMed