C. elegans ADARs promote organismal survival to pathogen infection
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PROVIDER: PRJNA929040 | ENA |
REPOSITORIES: ENA
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Project description:Here, we reveal that the Caenorhabditis elegans ADAR proteins promote survival of animals exposed to several opportunistic human pathogens. Our data indicate that ADARs help maintain proper levels of cuticular collagen genes, which in turn affects defense of the nematode to these bacteria.
2023-04-01 | GSE223919 | 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: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.
2012-04-05 | GSE28888 | GEO
Project description:Adenosine deaminases that act on RNA (ADARs) catalyze the conversion of adenosine to inosine in dsRNA. C. elegans ADARs, ADR-1 and ADR-2, promote the expression of genes containing dsRNA structures by preventing their processing into siRNAs and silencing by RNAi. The 26G endogenous siRNA (endo-siRNA) pathway generates a subset of siRNAs distinct from those made in adr-1;adr-2 mutants, but using many of the same factors. We found that adr-1;adr-2;rrf-3 mutants, lacking both ADARs and the RNA-dependent RNA polymerase RRF-3 required for the 26G pathway, display a bursting phenotype rescued by the RNAi factors RDE-1 and RDE-4. To determine what gene expression changes underlie the synthetic phenotype of adr-1;adr-2;rrf-3 mutants, we sequenced poly(A)+ RNA from adr-1;adr-2;rrf-3 embryos, their parent strains, and strains rescued with mutations in rde-1 and rde-4. We found that genes associated with edited structures were robustly downregulated in adr-1;adr-2;rrf-3 mutants in a manner partially dependent on rde-1 and rde-4. Additionally, genes induced during Orsay virus infections were induced in rrf-3 mutants and further upregulated in adr-1;adr-2;rrf-3 mutants, again dependent in part on rde-1 and rde-4.
2018-02-23 | GSE106647 | GEO
Project description:Cellular RNAs containing double-stranded RNA (dsRNA) structures are subject to A-to-I RNA editing by the adenosine deaminases that act on RNA (ADARs). While A-to-I editing can alter mRNA coding potential, most editing is observed in non-coding sequences, the function of which remains poorly characterized. To correlate small RNA population with expression patterns of ADARs and hyperedited RNAs (editing-enriched regions: EERs) defined and characterized in a separate RNAseq analysis, we re-analyzed existing smallRNAseq datasets of a wildtype strain and a strain lacking ADARs (adr-1;adr-2). Analysis of primary siRNAs from mixed-stage worms revealed that ADARs impact siRNA biogenesis from EERs. We then analyzed primary and secondary RNAs mapping to EERs from embryo-stage or L4-stage worms and observed that ADAR effects on siRNA levels are dependent on developmental stage.
2018-02-23 | GSE89765 | GEO
Project description:Circular RNAs (circRNAs) are produced by head-to-tail back-splicing which is mainly facilitated by base-pairing of reverse complementary matches (RCMs) in circRNA flanking introns. Adenosine deaminases acting on RNA (ADARs) are known to bind double-stranded RNAs for adenosine to inosine (A-to-I) RNA editing. Here we characterize ADARs as potent regulators of circular transcriptome by identifying over a thousand of circRNAs regulated by ADARs in a bidirectional manner through and beyond their editing function. We found that editing can stabilize or destabilize secondary structures formed between RCMs via correcting A:C mismatches to I(G)-C pairs or creating I(G).U wobble pairs, respectively. We provided experimental evidence that editing also favors the binding of RNA-binding proteins such as PTBP1 to regulate back-splicing. These ADARs-regulated circRNAs which are ubiquitously expressed in multiple types of cancers, demonstrate high functional relevance to cancer. Our findings support a hitherto unappreciated bidirectional regulation of circular transcriptome by ADARs and highlights the complexity of cross-talk in RNA processing and its contributions to tumorigenesis.
2022-01-25 | GSE164681 | GEO
Project description:To understand the role of genetic makeup in organismal tolerance/susceptibility we compared the Caenorhabditis elegans transcriptome profiles with those of Drosophila melanogaster. In this study, we exposed both organisms, to a synthetic chemical and evaluated their response at the transcriptome level, to gain insights to molecular players/pathways underlying organismal tolerance/susceptibility to xenobiotics
2018-12-01 | GSE98164 | GEO
Project description:To understand the role of genetic makeup in organismal tolerance/susceptibility we compared the Caenorhabditis elegans transcriptome profiles with those of Drosophila melanogaster. In this study, we exposed both organisms, to a synthetic chemical and evaluated their response at the transcriptome level, to gain insights to molecular players/pathways underlying organismal tolerance/susceptibility to xenobiotics
2018-12-01 | GSE98165 | GEO
Project description:Adenosine deaminases acting on RNA (ADARs) impact diverse cellular processes and pathological conditions. While we possess important insights into their roles in adult tissues, their functions in early cell fate specification remain less understood. To address this, we devised a comprehensive framework to investigate ADARs in human development. We began by charting time-course RNA editing profiles in human organs from fetal to adult stages, enabling broad insights into RNA editing trends across diverse tissues. Next, we utilized hPSC differentiation to experimentally probe ADARs across specific tissue-types, harnessing brain organoids as neural specific, and teratomas as pan-tissue developmental models. We found that time-series teratomas faithfully recapitulated developmental trends observed in fetal tissue. Motivated by this, we conducted pan-tissue, single-cell CRISPR-KO screens of ADARs in teratomas to assess their role in cell-fate specification. Knocking out ADAR1 led to a global decrease in RNA editing across all germ-layers. Intriguingly, we observed a significant fitness defect in mesodermal tissues, and an enrichment of adipogenic cells, revealing a novel role for ADAR1 in mesenchymal differentiation. Collectively, we developed a multi-pronged framework charting time-resolved RNA editing profiles in fetal and fetal-like organ tissues, thereby shedding light on the role of ADARs in development and cell fate-specification.
2024-10-24 | GSE248941 | GEO
Project description:We engineered circular ADAR recruiting guide RNAs (cadRNAs) that efficiently recruit endogenous ADARs to edit specific sites on target RNA
2021-11-15 | GSE164956 | GEO