An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits
PKR activation

J 2024

An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits PKR activation

SINIGAGLIA, Ketty, Anna CHERIAN, Qiupei DU, Valentina LACOVICH STRAŠIL, Dragana VUKIĆ et. al.

Basic information

Original name

An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits PKR activation

Authors

SINIGAGLIA, Ketty (380 Italy, belonging to the institution), Anna CHERIAN (356 India, belonging to the institution), Qiupei DU (156 China, belonging to the institution), Valentina LACOVICH STRAŠIL (705 Slovenia, belonging to the institution), Dragana VUKIĆ (688 Serbia, belonging to the institution), Janka MELICHEROVÁ (703 Slovakia, belonging to the institution), Pavla MUSILOVÁ (203 Czech Republic, belonging to the institution), Lisa ZERAD, Stanislav STEJSKAL (203 Czech Republic, belonging to the institution), Radek MALIK, Jan PROCHAZKA, Nadege BONDURAND, Radislav SEDLACEK, Mary Anne O'CONNELL (372 Ireland, guarantor, belonging to the institution) and Liam KEEGAN (372 Ireland, belonging to the institution)

Edition

Cell Reports, CAMBRIDGE, Cell Press, 2024, 2211-1247

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 8.800 in 2022

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.celrep.2024.114618

UT WoS

001297074700001

Keywords in English

RNA; RECOGNITION; DIMERIZATION; ELF2-ALPHA

Abstract

V originále

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.

Links

EF17_043/0009632, research and development project

Name: CETOCOEN Excellence

GA19-16963S, research and development project

Name: Genetický model myši pro studium kontroly interferonu a zánětu

Investor: Czech Science Foundation

GA20-11101S, research and development project

Name: Objasnění úlohy RNA-editačního enzymu ADAR1 v nových biologických drahách a určení jeho postranslační regulace.

Investor: Czech Science Foundation

GX21-27329X, research and development project

Name: ADAR-dependentní RNA editace; Jak imunitní systém a mozek porušují Centrální Dogma.

Investor: Czech Science Foundation

90126, large research infrastructures

Name: CCP II

90250, large research infrastructures

Name: Czech-BioImaging III

90269, large research infrastructures

Name: RECETOX RI II

Citovat

SINIGAGLIA, Ketty, Anna CHERIAN, Qiupei DU, Valentina LACOVICH STRAŠIL, Dragana VUKIĆ, 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. 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.

@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.

Detailed Information on Publication Record