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Series GSE218545 Query DataSets for GSE218545
Status Public on Jun 07, 2023
Title Elevated pre-mRNA 3' end processing activity in cancer cells renders vulnerability to inhibition of cleavage and polyadenylation [ChrRNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Cleavage and polyadenylation (CPA) defines the 3’ end of almost all eukaryotic mRNAs. CPA inhibition, or CPAi, leads to transcriptional readthrough. Here, we show that the CPSF-73 inhibitor JTE-607 globally perturbs gene expression, especially for those with a high GC content and located in high gene density regions. Based on regulated alternative polyadenylation (APA) events, we found that more frequently used CPA sites are inhibited by JTE-607 to a greater extent. Consistently, cells with elevated CPA activities, as indicated by preferential usage of proximal APA sites, display greater transcriptional readthrough and gene expression disturbance upon JTE-607 treatment. Remarkably, overexpression of the core CPA factor FIP1 enhances global CPA activity in the cell and leads to greater JTE-607 sensitivity. Taken together, our data indicate that CPAi selectively impacts genes based on their genomic features and the CPA activity of a cell is a key determinant of sensitivity to CPAi.
 
Overall design For chromatin RNA sequencing, HeLa, HepG2, U937 and U937MP cells were treated with DMSO or 1 μM JTE-607 for 2 hrs before cells were collected for chromatin RNA extraction.
 
Contributor(s) Cui Y, Wang L, Ding Q, Shin J, Cassel J, Liu Q, Salvino JM, Tian B
Citation(s) 37528120
Submission date Nov 22, 2022
Last update date Sep 06, 2023
Contact name Bin Tian
E-mail(s) btian@wistar.org
Organization name The Wistar Institute
Street address 3601 Spruce Street
City Philadelphia
State/province Pennsylvania
ZIP/Postal code 19104
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (8)
GSM6751690 HeLa cells, DMSO ChrRNA-seq
GSM6751691 HeLa cells, 1uM JTE-607 ChrRNA-seq
GSM6751692 HepG2 cells, DMSO ChrRNA-seq
This SubSeries is part of SuperSeries:
GSE218557 Elevated pre-mRNA 3' end processing activity in cancer cells renders vulnerability to inhibition of cleavage and polyadenylation
Relations
BioProject PRJNA904279

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Supplementary file Size Download File type/resource
GSE218545_RAW.tar 2.2 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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