Τίτλος:
Adenosine-to-inosine RNA editing contributes to type I interferon responses in systemic sclerosis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objective: Adenosine deaminase acting on RNA-1 (ADAR1) enzyme is a type I interferon (IFN)-stimulated gene (ISG) catalyzing the deamination of adenosine-to-inosine, a process called A-to-I RNA editing. A-to-I RNA editing takes place mainly in Alu elements comprising a primate-specific level of post-transcriptional gene regulation. Whether RNA editing is involved in type I IFN responses in systemic sclerosis (SSc) patients remains unknown. Methods: ISG expression was quantified in skin biopsies and peripheral blood mononuclear cells derived from SSc patients and healthy subjects. A-to-I RNA editing was examined in the ADAR1-target cathepsin S (CTSS) by an RNA editing assay. The effect of ADAR1 on interferon-α/β-induced CTSS expression was assessed in human endothelial cells in vitro. Results: Increased expression levels of the RNA editor ADAR1, and specifically the long ADAR1p150 isoform, and its target CTSS are strongly associated with type I IFN signature in skin biopsies and peripheral blood derived from SSc patients. Notably, IFN-α/β-treated human endothelial cells show 8-10-fold increased ADAR1p150 and 23-35-fold increased CTSS expression, while silencing of ADAR1 reduces CTSS expression by 60-70%. In SSc patients, increased RNA editing rate of individual adenosines located in CTSS 3′ UTR Alu elements is associated with higher CTSS expression (r = 0.36–0.6, P < 0.05 for all). Similar findings were obtained in subjects with activated type I IFN responses including SLE patients or healthy subjects after influenza vaccination. Conclusion: ADAR1p150-mediated A-to-I RNA editing is critically involved in type I IFN responses highlighting the importance of post-transcriptional regulation of proinflammatory gene expression in systemic autoimmunity, including SSc. © 2021 The Authors
Συγγραφείς:
Vlachogiannis, N.I.
Tual-Chalot, S.
Zormpas, E.
Bonini, F.
Ntouros, P.A.
Pappa, M.
Bournia, V.-K.
Tektonidou, M.G.
Souliotis, V.L.
Mavragani, C.P.
Stamatelopoulos, K.
Gatsiou, A.
Sfikakis, P.P.
Stellos, K.
Περιοδικό:
Journal of Autoimmune Diseases
Εκδότης:
INSTAP Academic Press
DOI:
10.1016/j.jaut.2021.102755
