Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A90242%2F23%3A00133755" target="_blank" >RIV/00216224:90242/23:00133755 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S2211124722018009?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2211124722018009?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.celrep.2022.111901" target="_blank" >10.1016/j.celrep.2022.111901</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Direct observation of backtracking by influenza A and B polymerases upon consecutive incorporation of the nucleoside analog T1106

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

—

Návaznosti

—

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cell Reports

ISSN

2211-1247

e-ISSN

—

Svazek periodika

42

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

24

Strana od-do

1-24

Kód UT WoS článku

000964718900001

EID výsledku v databázi Scopus

2-s2.0-85147311380