|
|
GEO help: Mouse over screen elements for information. |
|
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 [QuantSeq-Pool] |
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 QuantSeq analysis, HeLa and HepG2 cells were treated with DMSO or JTE-607 (1μM or 10μM) for 8 hrs before harvest for total RNA extraction. U937 and U937MP cells were treated with DMSO or 1 μM JTE-607 for 7 hrs before total 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 |
May 02, 2023 |
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)
|
GSM7287685 |
U937/iFIP1, Dox-, DMSO, QuantSeq-Pool, read 1 |
GSM7287686 |
U937/iFIP1, Dox-, DMSO, QuantSeq-Pool, read 2 |
GSM7287687 |
U937/iFIP1, Dox-, 1uM JTE-607, QuantSeq-Pool, read 1 |
GSM7287688 |
U937/iFIP1, Dox-, 1uM JTE-607, QuantSeq-Pool, read 2 |
GSM7287689 |
U937/iFIP1, Dox+, DMSO, QuantSeq-Pool, read 1 |
GSM7287690 |
U937/iFIP1, Dox+, DMSO, QuantSeq-Pool, read 2 |
GSM7287691 |
U937/iFIP1, Dox+, 1uM JTE-607, QuantSeq-Pool, read 1 |
GSM7287692 |
U937/iFIP1, Dox+, 1uM JTE-607, QuantSeq-Pool, read 2 |
|
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 |
PRJNA966236 |
Supplementary file |
Size |
Download |
File type/resource |
GSE231527_RAW.tar |
3.5 Mb |
(http)(custom) |
TAR (of CSV, TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
|
|
|
|
|