| KOUBA, Tomas, Anna DUBANKOVA, Petra DRNCOVA, Elisa DONATI, Pietro VIDOSSICH, Valentina SPERANZINI, Alex PFLUG, Johanna HUCHTING, Chris MEIER, De Vivo MARCO and Stephen CUSACK. Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106. Cell Reports. CAMBRIDGE: Cell Press, 2023, vol. 42, No 1, p. 1-24. ISSN 2211-1247. Available from: https://dx.doi.org/10.1016/j.celrep.2022.111901. |
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@article{2383037,
author = {Kouba, Tomas and Dubankova, Anna and Drncova, Petra and Donati, Elisa and Vidossich, Pietro and Speranzini, Valentina and Pflug, Alex and Huchting, Johanna and Meier, Chris and Marco, De Vivo and Cusack, Stephen},
article_location = {CAMBRIDGE},
article_number = {1},
doi = {http://dx.doi.org/10.1016/j.celrep.2022.111901},
keywords = {T-705 FAVIPIRAVIR; TRANSCRIPTION; RNA polymerase; REPLICATION; INFECTIONS; CryoEM; pyr-azinecarboxamide base analogs},
language = {eng},
issn = {2211-1247},
journal = {Cell Reports},
title = {Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106},
url = {https://www.sciencedirect.com/science/article/pii/S2211124722018009?via%3Dihub},
volume = {42},
year = {2023}
}
TY - JOUR
ID - 2383037
AU - Kouba, Tomas - Dubankova, Anna - Drncova, Petra - Donati, Elisa - Vidossich, Pietro - Speranzini, Valentina - Pflug, Alex - Huchting, Johanna - Meier, Chris - Marco, De Vivo - Cusack, Stephen
PY - 2023
TI - Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106
JF - Cell Reports
VL - 42
IS - 1
SP - 1-24
EP - 1-24
PB - Cell Press
SN - 22111247
KW - T-705 FAVIPIRAVIR
KW - TRANSCRIPTION
KW - RNA polymerase
KW - REPLICATION
KW - INFECTIONS
KW - CryoEM
KW - pyr-azinecarboxamide base analogs
UR - https://www.sciencedirect.com/science/article/pii/S2211124722018009?via%3Dihub
N2 - The antiviral pseudo-base T705 and its de-fluoro analog T1106 mimic adenine or guanine and can be compet-itively incorporated into nascent RNA by viral RNA-dependent RNA polymerases. Although dispersed, single pseudo-base incorporation is mutagenic, consecutive incorporation causes polymerase stalling and chain termination. Using a template encoding single and then consecutive T1106 incorporation four nucleotides later, we obtained a cryogenic electron microscopy structure of stalled influenza A/H7N9 polymerase. This shows that the entire product-template duplex backtracks by 5 nt, bringing the singly incorporated T1106 to the +1 position, where it forms an unexpected T1106:U wobble base pair. Similar structures show that influ-enza B polymerase also backtracks after consecutive T1106 incorporation, regardless of whether prior single incorporation has occurred. These results give insight into the unusual mechanism of chain termination by pyr-azinecarboxamide base analogs. Consecutive incorporation destabilizes the proximal end of the product -template duplex, promoting irreversible backtracking to a more energetically favorable overall configuration.
ER -
KOUBA, Tomas, Anna DUBANKOVA, Petra DRNCOVA, Elisa DONATI, Pietro VIDOSSICH, Valentina SPERANZINI, Alex PFLUG, Johanna HUCHTING, Chris MEIER, De Vivo MARCO and Stephen CUSACK. Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106. \textit{Cell Reports}. CAMBRIDGE: Cell Press, 2023, vol.~42, No~1, p.~1-24. ISSN~2211-1247. Available from: https://dx.doi.org/10.1016/j.celrep.2022.111901.
|
