Identification of specific binding sites of ADR-1 in vivo
Ontology highlight
ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE318525 | GEO | 2026/02/10
REPOSITORIES: GEO
Similar Datasets
Project description:Caenorhabditis elegans strain:N2, adr-1, adr-2, adr-1 adr-2 Transcriptome or Gene expression
| PRJNA82293 | ENA
Project description:Using a combination of molecular and genomic approaches we uncover a molecular mechanism that regulates RNA editing in a neural- and development-specific manner. We de novo identified 570 A-to-i editing sites in adult neural RNA-seq data and 6202 sites from re-analyzing L1 neural RNA seq.Comparing editomes during development led to the identification of both neural transcripts that were edited only in one life-stage. The stage-specific editing is largely regulated by differential gene expression during neural development, and proper gene expression of nearly one-third of these differentially expressed genes is dependent on adr-2, the only known A-to-I editing enzyme in C. elegans. However, we also identified a subset of neural transcripts which are edited and expressed throughout development. Interestingly, despite a neural-specific downregulation of adr-2 during development, the majority of sites edited throughout development exhibit increased editing in adult neural cells. Biochemical data suggests that ADR-1, a deaminase deficient member of the Adenosine deaminase acting on RNA (ADAR) family is competing with ADR-2 for binding to specific transcripts early in development. Our data suggest a model where during neural development, ADR-2 levels overcome ADR-1 repression, resulting in increased ADR-2 binding and editing of specific transcripts. Together, our findings reveal tissue- and development-specific regulation of RNA editing and identify a molecular mechanism that regulates ADAR substrate recognition and editing efficiency.
2020-06-06 | GSE151916 | GEO
Project description:Purpose: The purpose of this experiment is to expand the repertoire of C. elegans edited transcripts and identify the roles of ADR-1 as indirect regulator of editing and ADR-2 as the only active deaminase in vivo. Methods: Strand-specific RNA sequencing of wild-type and adr mutant worms, followed by a novel RNA variant calling and comparative analysis pipeline. Results: Despite lacking deaminase function, ADR-1 affects editing of over 60 adenosines within the 3’ UTRs of 16 different mRNAs. Furthermore, ADR-1 interacts directly with ADR-2 substrates, even in the absence of ADR-2; and mutations within its dsRNA binding domains abolished both binding and editing regulation. Conclusions: ADR-1 acts as a major regulator of editing by binding ADR-2 substrates in vivo and raises the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing by deaminase-independent mechanisms. Strand-specific RNA sequencing of wild-type and adr mutant worms, followed by a novel RNA variant calling and comparative analysis pipeline.
2014-01-20 | E-GEOD-51556 | biostudies-arrayexpress
Project description:Purpose: The purpose of this experiment is to expand the repertoire of C. elegans edited transcripts and identify the roles of ADR-1 as indirect regulator of editing and ADR-2 as the only active deaminase in vivo. Methods: Strand-specific RNA sequencing of wild-type and adr mutant worms, followed by a novel RNA variant calling and comparative analysis pipeline. Results: Despite lacking deaminase function, ADR-1 affects editing of over 60 adenosines within the 3’ UTRs of 16 different mRNAs. Furthermore, ADR-1 interacts directly with ADR-2 substrates, even in the absence of ADR-2; and mutations within its dsRNA binding domains abolished both binding and editing regulation. Conclusions: ADR-1 acts as a major regulator of editing by binding ADR-2 substrates in vivo and raises the possibility that other dsRNA binding proteins, including the inactive human ADARs, regulate RNA editing by deaminase-independent mechanisms.
2014-01-20 | GSE51556 | GEO
Project description:Adenosine deaminases that act on RNA (ADARs) are RNA editing enzymes that convert adenosine to inosine in double-stranded RNA (dsRNA). To evaluate effects of ADARs on small RNAs that derive from dsRNA precursors, we performed deep-sequencing, comparing small RNAs from wildtype and ADAR mutant C. elegans. While editing in small RNAs was rare, at least 40% of microRNAs had altered levels in at least one ADAR mutant strain, and miRNAs with significantly altered levels had mRNA targets with correspondingly affected levels. About 40% of siRNAs derived from endogenous genes (endo-siRNAs) also had altered levels in at least one mutant strain, including 63% of Dicer-dependent endo-siRNAs. The 26G class of endo-siRNAs was significantly affected by ADARs, and many altered 26G loci had intronic reads, and histone modifications associated with transcriptional silencing. Our data indicate ADARs, through both direct and indirect mechanisms, are important for maintaining wildtype levels of many small RNAs in C. elegans. Deep sequencing of small RNAs in wild-type (N2), adr-1 null, adr-2 null and adr-1;adr-2 null mixed stage C. elegans
2012-04-04 | E-GEOD-28888 | biostudies-arrayexpress
Project description:Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR)
| PRJNA208619 | ENA
Project description:Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR) [expression]
| PRJNA208432 | ENA
Project description:Global regulation of alternative splicing by adenosine deaminase acting on RNA (ADAR) [RNA-seq]
| PRJNA208620 | ENA
Project description:Exogenous RNA, such as circRNA, could be edited by endogenous editors, such as C-to-U editor activation-induced deaminase and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (AID/APOBEC), and A-to-I editor Adenosine deaminases acting on RNA (ADAR) (I: inosine, recognized as G). Editing of circRNA may interfere with IRES and Kozak sequence to initiate antigen translation, and may alter antigen products or mutate stop codons.
2023-12-31 | GSE221086 | GEO
Project description:RNA editing can be a promising therapeutic approach. However, ectopic expression of RNA editing enzymes was found to trigger off-target editing, and the recruitment of endogenous adenosine deaminase acting on RNA (ADAR) suffers from low efficiency and fluctuating ADAR expression. Here, we identified ADAR inhibitors (ADIs) that suppressed the activity of the fused ADAR2 deaminase domain (ADAR2DD). Using ADI, we developed an RNA transformer adenine base editor (RtABE) with both high specificity and high efficiency. With the fusion of ADI to ADAR2DD, RtABE remains inactive until it binds its target site. After binding to the target site, ADI is cleaved from ADAR2DD and RtABE becomes active. RtABE induced efficient on-target editing in various cells with different ADAR expression levels. Delivering RtABE via an adeno-associated virus enabled up to a 45% RNA correction rate in Hurler syndrome mice with no significant off-target editing, and -L-iduronidase activity was restored. RtABE is a highly specific and efficient RNA editing system with broad applicability.
2025-02-06 | GSE267726 | GEO