Measuring the influence of RNA binding proteins on A-to-I RNA editing in the Drosophila brain
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ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE126628 | GEO | 2019/05/08
REPOSITORIES: GEO
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Project description:We performed RNA-seq to profile gene expression in the heads and whole bodies of 32 isofemale fly lines from two divergent microclimates at 'Evolution Canyon' in Israel (16 fly lines from each microclimate). We also measured RNA editing levels in the head tissue of these flies.
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Project description:The RNA editing enzyme ADAR chemically modifies adenosine (A) to inosine (I), which is interpreted by the ribosome as a guanosine. Here we assess cotranscriptional A-to-I editing in Drosophila, by isolating nascent RNA from adult fly heads and subjecting samples to high-throughput sequencing. There are a large number of edited sites within nascent exons. Nascent RNA from an ADAR null mutant strain was also sequenced, indicating that almost all A-to-I events require ADAR. Moreover, mRNA editing levels correlate with editing levels within the cognate nascent RNA sequence, indicating that the extent of editing is set cotranscriptionally. Surprisingly, the nascent data also identify an excess of intronic over exonic editing sites. These intronic sites occur preferentially within introns that are poorly spliced cotranscriptionally, suggesting a link between editing and splicing. We conclude that ADAR-mediated editing is more widespread than previously indicated and largely occurs cotranscriptionally. GSM914095: Fly genomic DNA sequencing. Sequenced on the Illumina GA II. GSM914102-GSM914113: Fly head nascent RNA profiles over 6 time points of a 12hr light:dark cycle in duplicate; sequenced on the Illumina GA II. GSM914114-GSM914119: Fly head nascent RNA profiles of yw, FM7, ADAR0 males in duplicate; sequenced on the HiSeq2000. GSM915213-GSM915214: Fly head mRNA profiles over 2 time points of a 12hr light:dark cycle; sequenced on the Illumina GA II. GSM915215-GSM915220: Fly head mRNA profiles over 6 time points of a 12hr light:dark cycle; paired-end sequenced on the Illumina GA II. GSM915221-GSM91526: Fly head mRNA profiles over 6 time points of a 12hr light:dark cycle; sequenced on the Illumina GA II.
2012-05-31 | E-GEOD-37232 | biostudies-arrayexpress
Project description:We applied microfluidic multiplex PCR and deep sequencing (mmPCR-seq) to quantify RNA editing levels at targeted sites in 32 isofemale lines from two divergent microclimates at 'Evolution Canyon' in Israel (16 fly lines from each microclimate). Editing levels were compared between different populations at 25˚C , and were also compared between 25˚C and 18˚C within populations.
2017-09-20 | GSE104084 | GEO
Project description:We report the application of mmPCR-seq to male whole body samples from 131 strains of the DGRP. We quantified RNA editing at 605 different loci using a microfluidic multiplex PCR method coupled with deep sequencing. RT-PCR amplification of 605 loci from 131 fly strains to quantify RNA editing levels.
2015-08-06 | E-GEOD-67082 | biostudies-arrayexpress
Project description:Autism spectrum disorder (ASD) is a neurodevelopmental disease with complex heterogeneity and aberrations in multiple levels of neurobiology. Recently, our understanding of the molecular abnormalities in ASD has been greatly expanded through transcriptomic analyses of postmortem brains. However, a crucial molecular pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled the global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of ASD cortices and cerebella. Strikingly, we observed a global bias of hypoediting in ASD brains, common to different brain regions and involving many genes with critical neurological function. The large-scale RNA editing changes allowed us to reveal novel insights of RNA editing regulation. Through genome-wide protein-RNA binding analyses and detailed molecular assays, we show that the Fragile X proteins, FMRP and FXR1P, interact with ADAR protens and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA editing alterations between ASD and Fragile X syndrome, thus establishing RNA editing as a novel molecular link underlying these two highly related diseases. Our findings support a role for RNA editing dysregulation in ASD pathophysiology and highlight novel mechanisms for RNA editing regulation.
2018-12-14 | GSE107867 | GEO
Project description:Autism spectrum disorder (ASD) is a neurodevelopmental disease with complex heterogeneity and aberrations in multiple levels of neurobiology. Recently, our understanding of the molecular abnormalities in ASD has been greatly expanded through transcriptomic analyses of postmortem brains. However, a crucial molecular pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled the global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of ASD cortices and cerebella. Strikingly, we observed a global bias of hypoediting in ASD brains, common to different brain regions and involving many genes with critical neurological function. The large-scale RNA editing changes allowed us to reveal novel insights of RNA editing regulation. Through genome-wide protein-RNA binding analyses and detailed molecular assays, we show that the Fragile X proteins, FMRP and FXR1P, interact with ADAR protens and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA editing alterations between ASD and Fragile X syndrome, thus establishing RNA editing as a novel molecular link underlying these two highly related diseases. Our findings support a role for RNA editing dysregulation in ASD pathophysiology and highlight novel mechanisms for RNA editing regulation.
2018-12-14 | GSE117776 | GEO
Project description:The project aims to evaluate the contribution of ADAR1 RNA editing to B cell lymphomagenesis, specifically in diffuse large B cell lymphoma (DLBCL). Within our DLBCL cohort, RNA editing targets transcripts within known lymphoma-driving pathways such as apoptosis, p53 and NF-kB signaling, as well as the previously unrecognized RIG-I-like pathway. In the latter context, we show that ADAR1-mediated editing in the MAVS transcript correlates with increased MAVS protein expression levels, associating with increased interferon/NF-kB signaling and increased T cell exhaustion. To confirm this mechanism, we have performed LC-MSMS analysis on a DLBCL cell line (RCK8) in the presence or absence of ADAR1 (Figure S11D ). Additionally, using targeted RNA base editing tools to restore editing within MAVS 3'UTR in ADAR1-deficient cells, we demonstrate that editing is likely to be causal to an increase in downstream signaling in the absence of activation by canonical nucleic acid receptor sensing. To confirm that this signaling increase depends on an increase of MAVS protein upon specific editing, we have performed LC-MSMS analysis on the same samples (Figure 4G).
2023-07-20 | PXD041549 | Pride
Project description:Autism spectrum disorder (ASD) is a neurodevelopmental disease with complex heterogeneity and aberrations in multiple levels of neurobiology. Recently, our understanding of the molecular abnormalities in ASD has been greatly expanded through transcriptomic analyses of postmortem brains. However, a crucial molecular pathway involved in synaptic development, RNA editing, has not yet been studied on a genome-wide scale. Here we profiled the global patterns of adenosine-to-inosine (A-to-I) editing in a large cohort of ASD cortices and cerebella. Strikingly, we observed a global bias of hypoediting in ASD brains, common to different brain regions and involving many genes with critical neurological function. The large-scale RNA editing changes allowed us to reveal novel insights of RNA editing regulation. Through genome-wide protein-RNA binding analyses and detailed molecular assays, we show that the Fragile X proteins, FMRP and FXR1P, interact with ADAR protens and modulate A-to-I editing. Furthermore, we observed convergent patterns of RNA editing alterations between ASD and Fragile X syndrome, thus establishing RNA editing as a novel molecular link underlying these two highly related diseases. Our findings support a role for RNA editing dysregulation in ASD pathophysiology and highlight novel mechanisms for RNA editing regulation.
2018-12-14 | GSE107895 | GEO
Project description:The RNA editing enzyme ADAR chemically modifies adenosine (A) to inosine (I), which is interpreted by the ribosome as a guanosine. Here we assess cotranscriptional A-to-I editing in Drosophila, by isolating nascent RNA from adult fly heads and subjecting samples to high-throughput sequencing. There are a large number of edited sites within nascent exons. Nascent RNA from an ADAR null mutant strain was also sequenced, indicating that almost all A-to-I events require ADAR. Moreover, mRNA editing levels correlate with editing levels within the cognate nascent RNA sequence, indicating that the extent of editing is set cotranscriptionally. Surprisingly, the nascent data also identify an excess of intronic over exonic editing sites. These intronic sites occur preferentially within introns that are poorly spliced cotranscriptionally, suggesting a link between editing and splicing. We conclude that ADAR-mediated editing is more widespread than previously indicated and largely occurs cotranscriptionally.
2012-05-31 | GSE37232 | GEO
Project description:We used an improved INTACT (Isolation of Nuclei Tagged in A specific Cell Type) technique to isolate RNA from purified nuclei from different neuronal populations of the Drosophila brain. Using microfluidic multiplex PCR and sequencing (mmPCR-seq), we determined gene expression and A-to-I RNA editing levels at editing sites across nine distinct neuronal sub-populations and a pan-neuronal control.
2019-01-18 | GSE113662 | GEO