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Series GSE237465 Query DataSets for GSE237465
Status Public on Apr 16, 2024
Title Nuclear RNA homeostasis promotes systems-level coordination of cell fate and senescence
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Other
Summary Understanding cellular coordination remains a challenge despite knowledge of individual pathways. The RNA exosome, targeting a wide range of RNA substrates, is often downregulated in cellular senescence. Utilizing an auxin-inducible system, we observed that RNA exosome depletion in embryonic stem cells significantly affects the transcriptome and proteome, causing pluripotency loss and pre-senescence onset. Mechanistically, exosome depletion triggers acute nuclear RNA aggregation, disrupting nuclear RNA-protein equilibrium. This disturbance limits nuclear protein availability and hinders polymerase initiation and engagement, reducing gene transcription. Concurrently, it promptly disrupts nucleolar transcription, ribosomal processes, and nuclear exporting, resulting in translational shutdown. Prolonged exosome depletion induces nuclear structural changes resembling senescent cells, including aberrant chromatin compaction, chromocenter disassembly, and intensified heterochromatic foci. These effects suggest that dynamic turnover of nuclear RNA orchestrates crosstalk between essential processes to optimize cellular function. Disruptions in nuclear RNA homeostasis result in systemic functional decline, altering the cell state and promoting senescence.
 
Overall design To explore the systems-level function of RNA metabolism, we investigated the effects of depleting the RNA exosome over time in mouse embryonic stem cells using an auxin-inducible system. We established AID-FBEXOSC2 ESCs to deplete the essential exosome component, EXOSC2. Addition of the auxin analog indole-3-acetic acid (IAA) induced rapid degradation of EXOSC2 protein.
To investigate the impact of EXOSC2 on nuclear functions, we performed profiling of RNA subcellular localization, nascent transcription, gene expression, epigenetic landscape and chromatin organization in AID-FBEXOSC2 ESCs treated with IAA for a period of 20 hours.
All experiments were designed to reveal the differences between control and EXOSC2-depleted ESCs.
 
Contributor(s) Han X, Xing L, Shen X
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Jul 14, 2023
Last update date Apr 16, 2024
Contact name Xue Han
E-mail(s) xuehan89@126.com
Organization name Tsinghua University
Department School of Medicine
Lab Shen Xiaohua Lab
Street address Zhongguancun North Street
City Beijing
ZIP/Postal code 100084
Country China
 
Platforms (1)
GPL21273 HiSeq X Ten (Mus musculus)
Samples (139)
GSM7622011 EXOSC2 AID ESCs, RNA, 0 hr, rep1
GSM7622012 EXOSC2 AID ESCs, RNA, 0 hr, rep2
GSM7622013 EXOSC2 AID ESCs, RNA, 4 hr, rep1
Relations
BioProject PRJNA994978

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE237465_EXOSC2_AID_ESCs_H3K27ac_peaks_0hr.txt.gz 149.1 Kb (ftp)(http) TXT
GSE237465_EXOSC2_AID_ESCs_H3K27ac_peaks_4hr.txt.gz 187.2 Kb (ftp)(http) TXT
GSE237465_EXOSC2_AID_HiC_0hr.hic 804.1 Mb (ftp)(http) HIC
GSE237465_EXOSC2_AID_HiC_20hr.hic 815.8 Mb (ftp)(http) HIC
GSE237465_EXOSC2_AID_HiC_4hr.hic 794.2 Mb (ftp)(http) HIC
GSE237465_RAW.tar 12.6 Gb (http)(custom) TAR (of BW)
GSE237465_gene_expression_profile_of_EXOSC2_AID_ESCs.txt.gz 1.5 Mb (ftp)(http) TXT
GSE237465_gene_expression_profile_of_EXOSC2_AID_RA_differentiation.txt.gz 2.0 Mb (ftp)(http) TXT
GSE237465_gene_expression_profile_of_EXOSC2_AID_RNPmesh.txt.gz 1.5 Mb (ftp)(http) TXT
GSE237465_gene_expression_profile_of_EXOSC2_AID_iMEFs.txt.gz 1.5 Mb (ftp)(http) TXT
GSE237465_gene_expression_profile_of_EXOSC2_AID_nascent_EU.txt.gz 1.6 Mb (ftp)(http) TXT
GSE237465_gene_expression_profile_of_EXOSC2_AID_subcellular_fractions.txt.gz 2.3 Mb (ftp)(http) TXT
GSE237465_gene_expression_profile_of_EXOSC2_AID_sucrose_fractions.txt.gz 2.4 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file
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