ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA
stability

J 2026

ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA stability

VUKIĆ, Dragana; Qiupei DU; Anna CHERIAN; Damiano AMORUSO; Květoslava BROŽINOVÁ et al.

Základní údaje

Originální název

ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA stability

Autoři

Vydání

NUCLEIC ACIDS RESEARCH, Oxford University Press, 2026, 0305-1048

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 13.100 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

ADAR1; ADAR2

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 8. 6. 2026 10:42, Mgr. Eva Dubská

Anotace

V originále

The adenosine deaminase acting on RNA (ADAR) enzymes deaminate adenosine to inosine in double-stranded (ds)RNA. Mammals express two catalytically active enzymes: ADAR1, which is ubiquitously expressed and essential for innate immune homeostasis, and ADAR2, which is enriched in the brain and vascular system. Here, we investigate the ADAR2 interactome and uncover a shared interaction network with ADAR1, including multiple components of the RNA exosome complex, a multi-subunit RNase involved in RNA processing, turnover, and surveillance. The interactions between ADARs and RNA exosome components are nuclear, and resistance to RNase A treatment implies their close proximity. We validated these interactions by immunoprecipitation of both endogenous and epitope-tagged ADAR proteins in multiple cell lines and mapped the interaction interfaces to their dsRNA-binding domains. Exploiting an MS2-MCP tethering system, we show that recruitment of ADAR1 or ADAR2 to the 3' UTR of a reporter transcript decreases its stability. This decrease in RNA levels was reversed when EXOSC3 was depleted, demonstrating that this destabilizing effect of ADARs on RNA is via the RNA exosome complex. Finally, knockdown of ADARs perturbs rRNA processing, a canonical function of the nuclear exosome, demonstrating a cellular consequence of disrupting ADAR-exosome interactions.

Citovat

VUKIĆ, Dragana; Qiupei DU; Anna CHERIAN; Damiano AMORUSO; Květoslava BROŽINOVÁ; Ludivine WACHEUL; Valentina LACOVICH STRAŠIL; Christiane ZORBAS; Leena YADAV; Jiří SEDMÍK; Salla KESKITALO; Khadija HAJJI; Stanislav STEJSKAL; Markku VARJOSALO; Denis LAFONTAINE; Liam KEEGAN a Mary Anne O'CONNELL. ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA stability. NUCLEIC ACIDS RESEARCH. Oxford University Press, 2026, Volume 54, Issue 8, s. 1-20. ISSN 0305-1048. Dostupné z: https://doi.org/10.1093/nar/gkag381.

@article{2577119,
   author = {Vukić, Dragana and Du, Qiupei and Cherian, Anna and Amoruso, Damiano and Brožinová, Květoslava and Wacheul, Ludivine and Lacovich Strašil, Valentina and Zorbas, Christiane and Yadav, Leena and Sedmík, Jiří and Keskitalo, Salla and Hajji, Khadija and Stejskal, Stanislav and Varjosalo, Markku and Lafontaine, Denis and Keegan, Liam and O'Connell, Mary Anne},
   article_number = {Issue 8},
   doi = {https://doi.org/10.1093/nar/gkag381},
   keywords = {ADAR1; ADAR2},
   language = {eng},
   issn = {0305-1048},
   journal = {NUCLEIC ACIDS RESEARCH},
   title = {ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA stability},
   url = {https://academic.oup.com/nar/article/54/8/gkag381/8661656},
   volume = {Volume 54},
   year = {2026}
}

TY  - JOUR
ID  - 2577119
AU  - Vukić, Dragana - Du, Qiupei - Cherian, Anna - Amoruso, Damiano - Brožinová, Květoslava - Wacheul, Ludivine - Lacovich Strašil, Valentina - Zorbas, Christiane - Yadav, Leena - Sedmík, Jiří - Keskitalo, Salla - Hajji, Khadija - Stejskal, Stanislav - Varjosalo, Markku - Lafontaine, Denis - Keegan, Liam - O'Connell, Mary Anne
PY  - 2026
TI  - ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA stability
JF  - NUCLEIC ACIDS RESEARCH
VL  - Volume 54
IS  - Issue 8
SP  - 1-20
EP  - 1-20
PB  - Oxford University Press
SN  - 03051048
KW  - ADAR1
KW  - ADAR2
UR  - https://academic.oup.com/nar/article/54/8/gkag381/8661656
N2  - The adenosine deaminase acting on RNA (ADAR) enzymes deaminate adenosine to inosine in double-stranded (ds)RNA. Mammals express two catalytically active enzymes: ADAR1, which is ubiquitously expressed and essential for innate immune homeostasis, and ADAR2, which is enriched in the brain and vascular system. Here, we investigate the ADAR2 interactome and uncover a shared interaction network with ADAR1, including multiple components of the RNA exosome complex, a multi-subunit RNase involved in RNA processing, turnover, and surveillance. The interactions between ADARs and RNA exosome components are nuclear, and resistance to RNase A treatment implies their close proximity. We validated these interactions by immunoprecipitation of both endogenous and epitope-tagged ADAR proteins in multiple cell lines and mapped the interaction interfaces to their dsRNA-binding domains. Exploiting an MS2-MCP tethering system, we show that recruitment of ADAR1 or ADAR2 to the 3' UTR of a reporter transcript decreases its stability. This decrease in RNA levels was reversed when EXOSC3 was depleted, demonstrating that this destabilizing effect of ADARs on RNA is via the RNA exosome complex. Finally, knockdown of ADARs perturbs rRNA processing, a canonical function of the nuclear exosome, demonstrating a cellular consequence of disrupting ADAR-exosome interactions.
ER  -

VUKI$\backslash$'C, Dragana; Qiupei DU; Anna CHERIAN; Damiano AMORUSO; Květoslava BROŽINOVÁ; Ludivine WACHEUL; Valentina LACOVICH STRAŠIL; Christiane ZORBAS; Leena YADAV; Jiří SEDMÍK; Salla KESKITALO; Khadija HAJJI; Stanislav STEJSKAL; Markku VARJOSALO; Denis LAFONTAINE; Liam KEEGAN a Mary Anne O'CONNELL. ADAR1 and ADAR2 associate with the RNA exosome and modulate RNA stability. \textit{NUCLEIC ACIDS RESEARCH}. Oxford University Press, 2026, Volume 54, Issue 8, s.~1-20. ISSN~0305-1048. Dostupné z: https://doi.org/10.1093/nar/gkag381.

Přehled o publikaci