Biological roles of A-to-I editing: implications in innate immunity, cell death, and cancer immunotherapy

Abstract

Adenosine-to-inosine (A-to-I) editing, a key RNA modification widely found in eukaryotes, is catalyzed by adenosine deaminases acting on RNA (ADARs). Such RNA editing destabilizes endogenous dsRNAs, which are subsequently recognized by the sensors of innate immune and other proteins as autologous dsRNAs. This prevents the activation of innate immunity and type I interferon-mediated responses, thereby reducing the downstream cell death induced by the activation of the innate immune sensing system. ADARs-mediated editing can also occur in mRNAs and non-coding RNAs (ncRNAs) in different species. In mRNAs, A-to-I editing may lead to missense mutations and the selective splicing of coding regions. Meanwhile, in ncRNAs, A-to-I editing may affect targeting and disrupt ncRNAs maturation, leading to anomalous cell proliferation, invasion, and responses to immunotherapy. This review highlights the biological functions of A-to-I editing, its role in regulating innate immunity and cell death, and its potential molecular significance in tumorigenesis and cancer targeted therapy and immunotherapy.

Full-length direct RNA sequencing reveals extensive remodeling of RNA expression, processing and modification in agingCaenorhabditis elegans

“…Furthermore, over 20% of the inosine edits located in 3’UTRs overlap potential microRNA binding sites (Table S9). As inosine has different base-pairing properties than adenosine 46 , these changes may alter the efficiency of microRNA targeting and regulation of these genes.…”

RNA editing in host lncRNAs as potential modulator in SARS-CoV-2 variants-host immune response dynamics

“…Chronic inflammatory circumstances increase RNA editing, which stabilizes proinflammatory transcripts and puts “fuel on the fire” for the ongoing inflammatory response. 55 Despite its potential impact on disease progression, the role of RNA editing in the host during an infection needs deeper investigation in different disease contexts. Recent studies on SARS-CoV-2 infection-mediated editing of host RNA have presented conflicting findings.…”

Cell death shapes cancer immunity: spotlighting PANoptosis

“…RIPK3, a member of the receptor interacting protein kinase family, interacts with RIPK1 to form necroptotic complexes, activating MLKL and initiating necroptosis, thereby repressing cancer development [ 36 , 53 ]. In addition, it has been found that RIPK3 can interact with ZBP1 receptor to mediate necroptosis and PANoptosis [ 54 ].…”