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@article{2436837,
author = {Sinigaglia, Ketty and Cherian, Anna and Du, Qiupei and Lacovich Strašil, Valentina and Vukić, Dragana and Melicherová, Janka and Musilová, Pavla and Zerad, Lisa and Stejskal, Stanislav and Malik, Radek and Prochazka, Jan and Bondurand, Nadege and Sedlacek, Radislav and O'Connell, Mary Anne and Keegan, Liam},
article_location = {CAMBRIDGE},
article_number = {8},
doi = {http://dx.doi.org/10.1016/j.celrep.2024.114618},
keywords = {RNA; RECOGNITION; DIMERIZATION; ELF2-ALPHA},
language = {eng},
issn = {2211-1247},
journal = {Cell Reports},
title = {An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits PKR activation},
url = {https://www.sciencedirect.com/science/article/pii/S2211124724009689?via%3Dihub},
volume = {43},
year = {2024}
}
TY - JOUR
ID - 2436837
AU - Sinigaglia, Ketty - Cherian, Anna - Du, Qiupei - Lacovich Strašil, Valentina - Vukić, Dragana - Melicherová, Janka - Musilová, Pavla - Zerad, Lisa - Stejskal, Stanislav - Malik, Radek - Prochazka, Jan - Bondurand, Nadege - Sedlacek, Radislav - O'Connell, Mary Anne - Keegan, Liam
PY - 2024
TI - An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits PKR activation
JF - Cell Reports
VL - 43
IS - 8
SP - 1-25
EP - 1-25
PB - Cell Press
SN - 22111247
KW - RNA
KW - RECOGNITION
KW - DIMERIZATION
KW - ELF2-ALPHA
UR - https://www.sciencedirect.com/science/article/pii/S2211124724009689?via%3Dihub
N2 - Adar null mutant mouse embryos die with aberrant double-stranded RNA (dsRNA)-driven interferon induction, and Adar Mavs double mutants, in which interferon induction is prevented, die soon after birth. Protein kinase R (Pkr) is aberrantly activated in Adar Mavs mouse pup intestines before death, intestinal crypt cells die, and intestinal villi are lost. Adar Mavs Eifak2 (Pkr) triple mutant mice rescue all defects and have longterm survival. Adenosine deaminase acting on RNA 1 (ADAR1) and PKR co-immunoprecipitate from cells, suggesting PKR inhibition by direct interaction. AlphaFold studies on an inhibitory PKR dsRNA binding domain (dsRBD)-kinase domain interaction before dsRNA binding and on an inhibitory ADAR1 dsRBD3PKR kinase domain interaction on dsRNA provide a testable model of the inhibition. Wild-type or editing- inactive human ADAR1 expressed in A549 cells inhibits activation of endogenous PKR. ADAR1 dsRNA binding is required for, but is not sufficient for, PKR inhibition. Mutating the ADAR1 dsRBD3-PKR contact prevents co-immunoprecipitation, ADAR1 inhibition of PKR activity, and co-localization of ADAR1 and PKR in cells.
ER -
SINIGAGLIA, Ketty, Anna CHERIAN, Qiupei DU, Valentina LACOVICH STRAŠIL, Dragana VUKI$\backslash$'C, Janka MELICHEROVÁ, Pavla MUSILOVÁ, Lisa ZERAD, Stanislav STEJSKAL, Radek MALIK, Jan PROCHAZKA, Nadege BONDURAND, Radislav SEDLACEK, Mary Anne O'CONNELL and Liam KEEGAN. An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits PKR activation. \textit{Cell Reports}. CAMBRIDGE: Cell Press, 2024, vol.~43, No~8, p.~1-25. ISSN~2211-1247. Available from: https://dx.doi.org/10.1016/j.celrep.2024.114618.
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