ADAR1 RNA editing regulates endothelial cell functions via the MDA-5 RNA sensing signaling pathway.
Adenosine Deaminase
/ genetics
Animals
Biomarkers
Endothelial Cells
/ metabolism
Gene Deletion
Gene Expression Regulation
Genes, Lethal
Immunity, Innate
Interferon-Induced Helicase, IFIH1
/ genetics
Mice
Mice, Knockout
Mice, Transgenic
RNA Editing
Repetitive Sequences, Nucleic Acid
Signal Transduction
Transcription, Genetic
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
12
08
2021
revised:
11
12
2021
accepted:
13
12
2021
entrez:
31
12
2021
pubmed:
1
1
2022
medline:
29
3
2022
Statut:
epublish
Résumé
The RNA-sensing signaling pathway has been well studied as an essential antiviral mechanism of innate immunity. However, its role in non-infected cells is yet to be thoroughly characterized. Here, we demonstrated that the RNA sensing signaling pathway also reacts to the endogenous cellular RNAs in endothelial cells (ECs), and this reaction is regulated by the RNA-editing enzyme ADAR1. Cellular RNA sequencing analysis showed that EC RNAs endure extensive RNA editing, especially in the RNA transcripts of short interspersed nuclear elements. The EC-specific deletion of ADAR1 dramatically reduced the editing level on short interspersed nuclear element RNAs, resulting in newborn death in mice with damage evident in multiple organs. Genome-wide gene expression analysis revealed a prominent innate immune activation with a dramatically elevated expression of interferon-stimulated genes. However, blocking the RNA sensing signaling pathway by deletion of the cellular RNA receptor MDA-5 prevented interferon-stimulated gene expression and rescued the newborn mice from death. This evidence demonstrated that the RNA-editing/RNA-sensing signaling pathway dramatically modulates EC function, representing a novel molecular mechanism for the regulation of EC functions.
Identifiants
pubmed: 34969816
pii: 5/3/e202101191
doi: 10.26508/lsa.202101191
pmc: PMC8739526
pii:
doi:
Substances chimiques
Biomarkers
0
ADAR1 protein, mouse
EC 3.5.4.4
Adenosine Deaminase
EC 3.5.4.4
Ifih1 protein, mouse
EC 3.6.1.-
Interferon-Induced Helicase, IFIH1
EC 3.6.4.13
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : RRD VA
ID : I01 RX001455
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK120531
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI139544
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG052912
Pays : United States
Informations de copyright
© 2021 Guo et al.
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