Elongation-Competent Pauses Govern the Fidelity of a Viral RNA-Dependent RNA Polymerase

Elongation-Competent Pauses Govern the Fidelity of a Viral RNA-Dependent RNA Polymerase

Dulin, D.
Vilfan, I.D.
Berghuis, B.A.
Hage, S.
Bamford, D.H.
Poranen, M.M.
Depken, S.M.
Dekker, N.H.

Applied Sciences

BN/Bionanoscience

2015-02-17

RNA viruses have specific mutation rates that balance the conflicting needs of an evolutionary response to host antiviral defenses and avoidance of the error catastrophe. While most mutations are known to originate in replication errors, difficulties of capturing the underlying dynamics have left the mechanochemical basis of viral mutagenesis unresolved. Here, we use multiplexed magnetic tweezers to investigate error incorporation by the bacteriophage ?6 RNA-dependent RNA polymerase. We extract large datasets fingerprinting real-time polymerase dynamics over four magnitudes in time, in the presence of nucleotide analogs, and under varying NTP and divalent cation concentrations and fork stability. Quantitative analysis reveals a new pause state that modulates polymerase fidelity and so ties viral polymerase pausing to the biological function of optimizing virulence. Adjusting the frequency of such pauses offers a target for therapeutics and may also reflect an evolutionary strategy for virus populations to track the gradual evolution of their hosts.

http://resolver.tudelft.nl/uuid:0561ab21-088b-4855-a22a-88e3c74265f3

https://doi.org/10.1016/j.celrep.2015.01.031

Elsevier (Cell Press)

2211-1247

Cell Reports, 10 (6), 2015

Institutional Repository

journal article

© 2015 The Authors
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/)