A-to-I editing and adr mutant gene expression in C. elegans germlines
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ABSTRACT:
ORGANISM(S): Caenorhabditis elegans
PROVIDER: GSE299666 | GEO | 2025/08/01
REPOSITORIES: GEO
Similar Datasets
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:A-to-I editing and adr mutant gene expression in C. elegans germlines
| PRJNA1275890 | ENA
Project description:A-to-I RNA editing is widespread in eukaryotic transcriptomes and plays an essential role in the creation of proteomic and phenotypic diversity. Loss of ADARs, the proteins responsible for A-to-I editing, results in lethality in mammals. In C. elegans, knocking out both ADARs, ADR-1 and ADR-2, results in aberrant behavior and abnormal development. Studies have shown that ADR-2 can actively deaminate dsRNA while ADR-1 cannot. However, as most studies of C. elegans ADARs were performed on worms mutated in both ADAR genes, the effects observed cannot be attributed to a single ADAR or to the interactions between ADAR genes. Therefore, we set to study the effects of each C. elegans ADAR on RNA editing, gene expression, protein levels and the contribution of each of ADAR to the phenotypes observed in worms mutated in both genes, in order to elucidate their distinct functions. We found significant differences in the phenotypes observed in worms mutated in a single ADAR gene. Worms harboring adr-1 mutations have a significant reduction in their lifespan, while worms harboring adr-2 mutations have extended lifespan. We also observed severe abnormalities in vulva formation mainly in adr-1 mutants, and we suggest that these phenotypes are a result of an RNA editing independent function of ADR-1. Mutations in each ADAR resulted in expressional changes in hundreds of genes, and a significant downregulation of edited genes. However, very few changes in the protein levels were observed. In addition, we found that ADR-1 binds many edited genes. Our results suggest that ADR-1 has a significant function in the RNA editing process and by altering editing levels it causes the severe phenotypes that we observed. In contrast, a complete lack of RNA editing is less harmful to the worms. Furthermore, our results indicate that the effect of RNA editing on the protein content in the cell is minor and probably the main purpose of these modifications is to antagonize or enhance other gene regulatory mechanisms that act on RNA.
2019-04-22 | GSE110701 | GEO
Project description:Caenorhabditis elegans strain:N2, adr-1, adr-2, adr-1 adr-2 Transcriptome or Gene expression
| PRJNA82293 | ENA
Project description:A high-throughput screen was performed to identify RNA binding proteins that impact fertility in Caenorhabditis elegans hermaphrodites. This screen makes use of animals expressing a vitellogenin (yolk protein) fusion with GFP, in a background (adr-2(-)) that corrects for a previously identified fertility defect in this strain. In addition to identifying several RNA binding proteins that regulate fertility, the screen also uncovered an interaction between the RNA binding proteins adr-2 and sqd-1, which were found to coregulate many transcripts important for fertility.
2023-12-01 | GSE244602 | GEO
Project description:ADAR proteins alter gene expression both via catalyzing adenosine-to-inosine RNA editing and in an editing-independent manner by binding to target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. To identify important neuronal targets in C. elegans, we performed the first unbiased assessment of the effects of ADR-2, the C. elegans editing enzyme, on the neural transcriptome. We identified the neural editome and gene expression changes associated with the loss of adr-2. As C. elegans lacking adr-2 exhibit reduced chemotaxis, our studies focused on targets that regulate this process. We identified an edited mRNA, clec-41, whose expression is dependent on ADR-2. Expressing clec-41 in adr-2 deficient neural cells restored chemotaxis. This study is the first of its kind in the RNA editing field to span from developing novel methodology for tissue-specific target identification to organismal behavior, significantly advancing our understanding of ADAR functions in neural cells.
2017-06-13 | GSE98869 | GEO
Project description:We generated RNA-seq libraries from three biological replicas of adbp-1 mutant worms at the embryo and L4 developmental stages. We wanted to identify editing sites globally in adbp-1 mutant worms and understand the preferable ADR-2 5’ and 3’ nearest neighbors of editing sites in wild-type worms in contrast to adbp-1 mutant worms. In addition, we wanted to test if the cytoplasmic localization of ADR-2 causes the downregulation of 3’UTR edited genes and lncRNAs, and test the effect of lacking ADBP-1 on global gene expression.
2024-07-03 | GSE230883 | 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: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