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

TitleAdar-mediated A-to-I editing is required for embryonic patterning and innate immune response regulation in zebrafish.
Publication TypeJournal Article
Year of Publication2022
AuthorsNiescierowicz, K, Pryszcz, L, Navarrete, C, Tralle, E, Sulej, A, Nahia, KAbu, Kasprzyk, MElżbieta, Misztal, K, Pateria, A, Pakuła, A, Bochtler, M, Winata, C
JournalNat Commun
Volume13
Issue1
Pagination5520
Date Published2022 Sep 20
ISSN2041-1723
KeywordsAdenosine, Animals, Immunity, Innate, Inosine, Mammals, RNA, RNA-Binding Proteins, 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.

DOI10.1038/s41467-022-33260-6
Alternate JournalNat Commun
Citation Key124
PubMed ID36127363
PubMed Central IDPMC9489775

Uncaught exception thrown in shutdown function.

PDOException: SQLSTATE[HY000]: General error: 8 attempt to write a readonly database: DELETE FROM {semaphore} WHERE (value = :db_condition_placeholder_0) ; Array ( [:db_condition_placeholder_0] => 20588525906703c15ac871c0.35937756 ) in lock_release_all() (line 269 of /home/lpryszcz/Public/zdg_lab_site/includes/lock.inc).