Adar-mediated A-to-I editing is required for embryonic patterning and innate immune response regulation in zebrafish

Abstract

Adenosine deaminases (ADARs) catalyze the deamination of adenosine to inosine, also known as A-to-I editing, in RNA. Although A-to-I editing occurs widely across animals and is well studied, new biological roles are still being discovered. Here, we study the role of A-to-I editing in early zebrafish development. We demonstrate that Adar, the zebrafish orthologue of mammalian ADAR1, is essential for establishing the antero-posterior and dorso-ventral axes and patterning. Genome-wide editing discovery reveals pervasive editing in maternal and the earliest zygotic transcripts, the majority of which occurred in the 3’-UTR. Interestingly, transcripts implicated in gastrulation as well as dorso-ventral and antero-posterior patterning are found to contain multiple editing sites. Adar knockdown or overexpression affect gene expression by 12 hpf. Analysis of adar-/- zygotic mutants further reveals that the previously described role of Adar in mammals in regulating the innate immune response is conserved in zebrafish. Our study therefore establishes distinct maternal and zygotic functions of RNA editing by Adar in embryonic patterning along the zebrafish antero-posterior and dorso-ventral axes, and in the regulation of the innate immune response, respectively.

Temporal landscape and translational regulation of A-to-I editing in mouse retina development

“…1B; Supplementary Table 1). This is in line with previous research findings 32,33 . Given that A-to-I editing is the most prevalent type of editing and has significant impacts on development 34–36 , we chose to focus our subsequent analysis solely on this type of editing.…”

“…Adar-mediated A-to-I editing has been established as crucial for normal development of organisms 33,43,44 . Disruptions to Adar can lead to serious consequences such as locomotion and neuron defects seen in flies with mutant Adar 45 .…”

Temporal landscape and translational regulation of A-to-I RNA editing in mouse retina development

“…1 B; Additional file 1 : Supplementary Tables 2 and 3). This proportion is in line with prior research findings [ 25 , 26 ]. Among these A-to-I editing sites, 8104 were previously reported by REDIportal, while the remaining 7005 were newly discovered, and both exhibited a similar motif pattern (Additional file 2 : Fig.…”

“…ADAR-mediated A-to-I editing has been established as crucial for the normal development of organisms [ 26 , 35 , 36 ]. Disruptions to ADAR can lead to serious consequences such as locomotion and neuron defects seen in flies with mutant ADAR [ 37 , 38 ].…”

Small but strong: the emerging role of small nucleolar RNA in cardiovascular diseases

“…In mammals, there are two common forms of RNA editing: A-to-I and cytidine to uridine (C-to-U). The former is catalysed by a family of enzymes called adenosine deaminases acting on RNA (ADARs) ( Figure 2D ) ( Yang et al, 2021 ; Niescierowicz et al, 2022 ). Recent evidence indicates the capacity of A-to-I editing to modulate snoRNA precursors.…”