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| 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
Other
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| 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.
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| 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.
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| 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 |
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| Submission date |
Mar 13, 2020 |
| Last update date |
May 30, 2022 |
| Contact name |
Michael Tellier |
| E-mail(s) |
mt477@leicester.ac.uk
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| Organization name |
University of Leicester
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| Department |
Department of Molecular and Cell Biology
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| Lab |
Tellier Lab
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| Street address |
Lancaster Road
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| City |
Leicester |
| State/province |
Select State |
| ZIP/Postal code |
LE1 7HB |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (20)
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| Relations |
| BioProject |
PRJNA612527 |
| SRA |
SRP252761 |
| 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 Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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