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.

Základní údaje

Originální název

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

Autoři

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.900

Kód RIV

RIV/00216224:14740/24:00137205

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1016/j.celrep.2024.114618

UT WoS

001297074700001

EID Scopus

2-s2.0-85201161071

Klíčová slova anglicky

RNA; RECOGNITION; DIMERIZATION; ELF2-ALPHA

Štítky

143160, CF CELLIM, CF GEN, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 2. 9. 2025 13:35, Valentina Lacovich Strašil, PhD

Anotace

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.

Návaznosti

EF17_043/0009632, projekt VaV

Název: CETOCOEN Excellence

GA19-16963S, projekt VaV

Název: Genetický model myši pro studium kontroly interferonu a zánětu

Investor: Grantová agentura ČR, A mouse genetic model to study the control of interferon and inflammation

GA20-11101S, projekt VaV

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

Investor: Grantová agentura ČR, Elucidating the role of the RNA editing enzyme ADAR1 in novel biological pathways and determine its posttranslational regulation.

GX21-27329X, projekt VaV

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

Investor: Grantová agentura ČR, ADAR RNA editing, how immune systems and brains breach The Central Dogma

90126, velká výzkumná infrastruktura

Název: CCP II

90250, velká výzkumná infrastruktura

Název: Czech-BioImaging III

90267, velká výzkumná infrastruktura

Název: NCMG III

90269, velká výzkumná infrastruktura

Název: 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 a Liam KEEGAN. An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits PKR activation. Cell Reports. CAMBRIDGE: Cell Press, 2024, roč. 43, č. 8, s. 1-25. ISSN 2211-1247. Dostupné z: https://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 = {https://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 a Liam KEEGAN. An ADAR1 dsRBD3-PKR kinase domain interaction on dsRNA inhibits PKR activation. \textit{Cell Reports}. CAMBRIDGE: Cell Press, 2024, roč.~43, č.~8, s.~1-25. ISSN~2211-1247. Dostupné z: https://doi.org/10.1016/j.celrep.2024.114618.

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