RNA modifications, alternative splicing and circular RNA landscape in the mouse brain: inosine and beyond [circRNA-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE271020 | GEO | 2025/12/02
REPOSITORIES: GEO
Similar Datasets
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:RNA modifications, including adenosine-to-inosine (A-to-I) editing, are fundamental for normal brain physiology, as they participate in multiple biological processes and pathological conditions. These modifications can alter RNA secondary structures and affinity for RNA-binding proteins, thereby influencing RNA processing mechanisms such as alternative splicing. In this study, we investigated A-to-I RNA editing and its impact on alternative splicing regulation in the mouse brain using ADAR enzyme-deficient mice. We analyzed the brain transcriptome of ADAR2 knockout (Adar2−/−Gria2R/R), as well as double ADAR1 catalytically inactive / ADAR2 knockout (Adar1E861A/E861A Ifih−/− Adar2−/−Gria2R/R) mice compared to wild-type controls, identifying alternative splicing events associated with the absence of ADAR1 and ADAR2 specific A-to-I editing.
2025-12-02 | GSE271019 | 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.
2012-04-05 | GSE28888 | GEO
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:Adenosine to inosine (A-to-I) RNA editing occurs in a wide range of tissues and cell types and can be catalyzed by one of two adenosine deaminase acting on double stranded RNA enzymes, ADAR and ADARB1. Editing can impact both coding and non-coding regions of RNA, and in higher organisms, has been proposed to function in adaptive evolution. Neither the prevalence of A-to-I editing nor the role of either ADAR or ADARB1 has been examined in the context of germ cell development in mammals. Computational analysis of whole testis and cell type specific RNA-sequencing data followed by molecular confirmation demonstrated that A-to-I RNA editing occurs in both the germ line and in somatic Sertoli cells in two targets, Cog3 and Rpa1. Expression analysis demonstrated both Adar and Adarb1 were expressed in both Sertoli cells and in a cell-type dependent manner during germ cell development. Conditional ablation of Adar did not impact testicular RNA editing in either germ cells or Sertoli cells. Additionally, Adar ablation in either cell type did not have gross impacts on germ cell development or male fertility. In contrast, global Adarb1 knockout animals demonstrated a complete loss of A-to-I RNA editing in spite of normal germ cell development. Taken together, these observations demonstrate ADARB1 mediates A-to-I RNA editing in the testis and these editing events are dispensable for male fertility in an inbred mouse strain in the lab.
2016-12-24 | GSE92870 | 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:Adenosine-to-inosine (A-to-I) RNA editing entails the enzymatic deamination of adenosines to inosines by adenosine deaminases acting on RNA (ADARs). Dysregulated A-to-I editing has been implicated in various diseases, including cancers. However, the precise factors governing the A-to-I editing and their physiopathological implications remain as a long-standing question. Herein, we unravel that DEAH box helicase 9 (DHX9), at least partially dependent of its helicase activity, functions as a bidirectional regulator of A-to-I editing in cancer cells. Intriguingly, the ADAR substrate specificity determines the opposing effects of DHX9 on editing as DHX9 silencing preferentially represses editing of ADAR1-specific substrates, whereas augments ADAR2-specific substrate editing. Analysis of 11 cancer types from The Cancer Genome Atlas (TCGA) reveals a striking overexpression of DHX9 in tumors. Further, tumorigenicity studies demonstrate a helicase-dependent oncogenic role of DHX9 in cancer development. In sum, DHX9 constitutes a bidirectional regulatory mode in A-to-I editing, which is in part responsible for the dysregulated editome profile in cancer.
2018-05-31 | GSE99789 | 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:Background: Adenosine deaminases that act on RNA (ADARs) bind to double-stranded and structured RNAs and deaminate adenosines to inosines. This A to I editing is widespread and required for normal life and development. Besides mRNAs and repetitive elements, ADARs can target miRNA precursors. Editing of miRNA precursors can affect processing efficiency and alter target specificity. Interestingly, ADARs can also influence miRNA abundance independent of RNA-editing. In mouse embryos where editing levels are low, ADAR2 was found to be the major ADAR protein that affects miRNA abundance. Here we extend our analysis to adult mouse brains where high editing levels are observed. Results: Using Illumina deep sequencing we compare the abundances of mature miRNAs and editing events within them, between wild-type and ADAR2 knockout mice in the adult mouse brain. Reproducible changes in abundance of specific miRNAs are observed in ADAR2 deficient mice. Most of these quantitative changes seem unrelated to A to I editing events. However, many A to G transitions in cDNAs prepared from mature miRNA sequences, reflecting A to I editing events in the RNA, are observed with frequencies reaching up to 80%. About half of these editing events are primarily caused by ADAR2 while a few miRNAs show increased editing in the absence of ADAR2, suggesting preferential editing by ADAR1. Moreover, novel, previously unknown editing events were identified in several miRNAs. In general 64% of all editing events are located within the seed region of mature miRNAs. In one of these cases retargeting of the edited miRNA could be verified in reporter assays. Also, altered processing efficiency upon editing near a processing site could be experimentally verified. Conclusions: ADAR2 can significantly influence the abundance of certain miRNAs in the brain. Only in a few cases changes in miRNA abundance can be explained by miRNA editing. Thus, ADAR2 binding to miRNA precursors, without editing them, may influence their processing and thereby abundance. ADAR1 and ADAR2 have both overlapping and distinct specificities for editing of miRNA editing sites. Over 60% of editing occurs in the seed region possibly changing target specificities for many edited miRNAs. Examination of the effect of ADAR2 on mature miRNA abundance and sequence in adult mouse brain.
2014-10-02 | E-GEOD-61066 | biostudies-arrayexpress
Project description:Adenosine to inosine (A-to-I) RNA editing is a highly conserved regulatory process carried out by adenosine deaminases (ADARs) on dsRNAs. Although a significant fraction of the transcriptome is edited, the function of most editing sites is unknown. Previous studies indicated changes in A-to-I RNA editing frequencies following exposure to several stress types. However, the overall effect of stress on the expression of ADAR targets is not fully understood. Here we performed high-throughput RNA sequencing of wildtype and ADAR mutant C. elegans worms after heat shock, to analyze the effect of heat shock stress on the expression pattern of genes. We found that ADAR regulation following heat shock does not involve directly heat shock related genes. Our analysis also revealed that, lncRNAs and pseudogenes, which have a tendency for secondary RNA structures, are enriched among upregulated genes upon heat shock in ADAR mutant worms, while they are downregulated in ADAR mutant worms under permissive conditions. Therefore, temperature increases may destabilize dsRNA structures and protect them from RNAi degradation, despite the lack of ADAR function. These findings shade a new light on the dynamics of gene expression under heat shock in relation to ADAR function.
2018-12-12 | GSE122015 | GEO