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Series GSE146970 Query DataSets for GSE146970
Status Public on Feb 04, 2022
Title RNase H2, mutated in Aicardi‐Goutières syndrome, resolves co-transcriptional R-loops to prevent DNA breaks and inflammation.
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary RNase H2 is a specialized enzyme that degrades RNA in RNA/DNA hybrids and deficiency of this enzyme causes a severe neuroinflammatory disease, Aicardi Goutières syndrome (AGS). However, the molecular mechanism underlying AGS is still unclear. Here, we show that RNase H2 is associated with a subset of genes, in a transcription-dependent manner where it interacts with RNA Polymerase II. RNase H2 depletion impairs transcription leading to accumulation of R-loops, structures that comprise RNA/DNA hybrids and a displaced DNA strand, mainly associated with short and intronless genes. Importantly, accumulated R-loops are processed by XPG and XPF endonucleases which leads to DNA damage and activation of the immune response, features associated with AGS. Consequently, we uncover a key role for RNase H2 in the transcription of human genes by maintaining R-loop homeostasis. Our results provide insight into the mechanistic contribution of R-loops to AGS pathogenesis.
Overall design In Hela cells: ChIP-seq of RNaseH2A and RNA polymerase II, DRIP-seq -/+ RNaseH after siLuc or siRNaseH2A, and chromatin RNA-seq after siLuc or siRNAseH2A.
Contributor(s) Cristini A, Tellier M, Constantinescu F, Accalai C, Albulescu LO, Heiringhoff R, Bery N, Sordet O, Murphy S, Gromak N
Citation(s) 35618715
Submission date Mar 13, 2020
Last update date May 30, 2022
Contact name Michael Tellier
Organization name University of Leicester
Department Department of Molecular and Cell Biology
Lab Tellier Lab
Street address Lancaster Road
City Leicester
State/province Select State
ZIP/Postal code LE1 7HB
Country United Kingdom
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (20)
GSM4411588 ChrSeq_siH2A_R1
GSM4411589 ChrSeq_siH2A_R2
GSM4411590 ChrSeq_siLuc_R1
BioProject PRJNA612527
SRA SRP252761

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Supplementary file Size Download File type/resource
GSE146970_DRIPseq_siLuc_Peaks.bed.gz 984.1 Kb (ftp)(http) BED
GSE146970_DRIPseq_siRNAseH2A_Peaks.bed.gz 930.0 Kb (ftp)(http) BED
GSE146970_RAW.tar 4.6 Gb (http)(custom) TAR (of BW)
GSE146970_RNaseH2A_ChIPseq_Peaks.bed.gz 174.1 Kb (ftp)(http) BED
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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