GEO series
RNA exonuclease REXO4 resolves m6A-marked R-loops and suppresses anti-tumor immunity [RNAseq]
GSE289625
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
28 samples
Submitted 2026/05/28
Platform GPL24676Platform GPL24247
Summary
Transcription blockage frequently occurs in tumor cells, and aberrant R-loop forming during this process drives genome instability. However, the regulation of R-loop homeostasis and its dysregulation in tumorigenesis are still under investigation. Here, we report that the RNA exonuclease REXO4 preserves genome stability by reducing excessive R-loops. Mechanistically, REXO4 resolves R-loops by 3’-5’ exonucleolytic cleavage of the RNA strand on RNA-DNA hybrids, where an accessible end is created by RNA endonuclease and N6-methyladenosine (m6A) modification on RNA moieties promotes REXO4 localization and R-loop removal. REXO4 ablation-induced DNA damage stimulates interferon response and tumor immune infiltration to suppress squamous cell carcinoma (SCC) growth and metastasis. Importantly, targeting the exonuclease activity of REXO4 via the inhibitor we developed synergizes with PD-1 blockade to inhibit SCC progression by recruiting and activating CD8+ T cells. Thus, our study provides mechanistic insight into how m6A couples with exonuclease in R-loop clearance and genome maintenance, and uncovers a druggable epi-transcriptional machinery that blocks innate immune response and enables SCC immune evasion.
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE289625_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 28 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1223845 and SRA study SRP563981. Searching any of these in the dataset finder brings you back here.
Study design
10 conditions, mostly in triplicate
SCC1_Ctrl_Vehicle ×3
SCC1_H151_iR4 ×3
SCC1_iR4 ×3
SCC1_KO_2_BX_795 ×3
SCC1_KO_2_H151 ×3
SCC1_R4KO_1_Vehicle ×3
SCC1_R4KO_2_Vehicle ×3
SCC1_Vehicle ×3
+2 more
Supports a between-group comparison across 28 samples.
10 replicated groups read from 28 sample titles; they account for 28 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8795339 Autochthonous_mouse_HNSCC_R4KO_Rep1
- GSM8795340 Autochthonous_mouse_HNSCC_R4KO_Rep2
- GSM8795341 Autochthonous_mouse_HNSCC_Wt_Rep1
- GSM8795342 Autochthonous_mouse_HNSCC_Wt_Rep2
- GSM8795343 SCC1_Ctrl_Vehicle_Rep1
- GSM8795344 SCC1_Ctrl_Vehicle_Rep2
- GSM8795345 SCC1_Ctrl_Vehicle_Rep3
- GSM8795346 SCC1_H151_iR4_Rep1
- GSM8795347 SCC1_H151_iR4_Rep2
- GSM8795348 SCC1_H151_iR4_Rep3
- GSM8795349 SCC1_iR4_Rep1
- GSM8795350 SCC1_iR4_Rep2
- GSM8795351 SCC1_iR4_Rep3
- GSM8795352 SCC1_KO_2_BX_795_Rep1
- GSM8795353 SCC1_KO_2_BX_795_Rep2
- GSM8795354 SCC1_KO_2_BX_795_Rep3
- GSM8795355 SCC1_KO_2_H151_Rep1
- GSM8795356 SCC1_KO_2_H151_Rep2
- GSM8795357 SCC1_KO_2_H151_Rep3
- GSM8795358 SCC1_R4KO_1_Vehicle_Rep1
- GSM8795359 SCC1_R4KO_1_Vehicle_Rep2
- GSM8795360 SCC1_R4KO_1_Vehicle_Rep3
- GSM8795361 SCC1_R4KO_2_Vehicle_Rep1
- GSM8795362 SCC1_R4KO_2_Vehicle_Rep2
- GSM8795363 SCC1_R4KO_2_Vehicle_Rep3
- GSM8795364 SCC1_Vehicle_Rep1
- GSM8795365 SCC1_Vehicle_Rep2
- GSM8795366 SCC1_Vehicle_Rep3
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