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| 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] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| 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.
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| Contributor(s) |
Cui Y, Wang L, Ding Q, Shin J, Cassel J, Liu Q, Salvino JM, Tian B |
| Citation(s) |
37528120 |
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| Submission date |
Nov 22, 2022 |
| Last update date |
Sep 06, 2023 |
| Contact name |
Bin Tian |
| E-mail(s) |
btian@wistar.org
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| Organization name |
The Wistar Institute
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| Street address |
3601 Spruce Street
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| City |
Philadelphia |
| State/province |
Pennsylvania |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (12)
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| GSM6752469 |
HepG2 cells, DMSO QuantSeq |
| GSM6752470 |
HepG2 cells, 1uM JTE-607 QuantSeq |
| GSM6752471 |
HepG2 cells, 10uM JTE-607 QuantSeq |
| GSM6752472 |
U937 cells, DMSO QuantSeq |
| GSM6752473 |
U937 cells, 1uM JTE-607 QuantSeq |
| GSM6752474 |
U937 cells with PMA, DMSO QuantSeq |
| GSM6752475 |
U937 cells with PMA, 1uM JTE-607 QuantSeq |
| GSM7287683 |
U937 cells, DMSO, rep2 QuantSeq |
| GSM7287684 |
U937 cells with PMA, DMSO, rep2 QuantSeq |
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| 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 |
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| Relations |
| BioProject |
PRJNA904306 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE218555_RAW.tar |
3.2 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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