Nucleic Acids Research Advance Access originally published online on November 5, 2008
Nucleic Acids Research 2008 36(22):7059-7067; doi:10.1093/nar/gkn836
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Nucleic Acids Research, 2008, Vol. 36, No. 22 7059-7067
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Nucleic Acid Enzymes |
Reinitiated viral RNA-dependent RNA polymerase resumes replication at a reduced rate
1Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands and 2Institute of Biotechnology and Department of Biological and Environmental Sciences, Viikki Biocenter, P.O. Box 56, 00014 University of Helsinki, Finland
*To whom correspondence should be addressed. Tel: +31 15 278 3219; Fax: +31 15 278 1202; Email: n.h.dekker{at}tudelft.nl
Received August 27, 2008. Accepted October 14, 2008.
RNA-dependent RNA polymerases (RdRP) form an important class of enzymes that is responsible for genome replication and transcription in RNA viruses and involved in the regulation of RNA interference in plants and fungi. The RdRP kinetics have been extensively studied, but pausing, an important regulatory mechanism for RNA polymerases that has also been implicated in RNA recombination, has not been considered. Here, we report that RdRP experience a dramatic, long-lived decrease in its elongation rate when it is reinitiated following stalling. The rate decrease has an intriguingly weak temperature dependence, is independent of both the nucleotide concentration during stalling and the length of the RNA transcribed prior to stalling; however it is sensitive to RNA structure. This allows us to delineate the potential factors underlying this irreversible conversion of the elongation complex to a less active mode.
Present address: Andrea Candelli, Department of Physics and Astronomy, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands
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