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| Status |
Public on Nov 22, 2018 |
| Title |
Acetylation of spliceosome protein PHF5A modulates stress responses and colorectal carcinogenesis through alternative splicing mediated upregulation of KDM3A |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The process utilized by cancer cells for adapting to cellular stress is a key point for carcinogenesis. Alternative pre-mRNA splicing induced post-transcriptional gene expression regulation is one of the pathways for tumors maintaining proliferation rates accompanying the malignant phenotype under stress. However, the protein post-translational modification, especially protein acetylation on pre-mRNA splicing processes under stress is unknown. Here, we uncovered a list of hyperacetylated proteins in the context of acutely reduced Acetyl-CoA levels under nutrient starvation. PHD finger-like domain-containing protein 5A (PHF5A/SF3b14b), a component of U2 snRNPs, can be acetylated at lysine 29 in response to multiple cellular stresses. P300 and HDAC6 regulate PHF5A acetylation levels. PHF5A acetylation strengthens the interaction among U2 snRNPs, and affects global pre-mRNA splicing pattern and extensive gene expression. PHF5A hyperacetylation induced alternative splicing stabilizes KDM3A mRNA and promotes its protein expression. Pathologically, PHF5A K29 hyperacetylation and KDM3A upregulation axis are correlated with poor prognosis of colon cancer patients. Our findings uncovered a novel mechanism of anti-stress pathway that acetylation on PHF5A promotes the cancer cells capacity for stress resistance and consequently contributes to colon carcinogenesis.
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| Overall design |
6 samples. HCT116 colon cancer cells were stable expression PHF5A WT or PHF5A K29Q, Cells' RNA was harvested using Trizol reagent. 3 ug of total RNA is used for the construction of sequencing libraries by Hiseq 4000 PE150.
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| Web link |
https://www.sciencedirect.com/science/article/pii/S1097276519302795?via%3Dihub
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| |
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| Contributor(s) |
Wang Z, Yang X, Luo J |
| Citation(s) |
31054974 |
| |
| Submission date |
Nov 20, 2018 |
| Last update date |
Feb 20, 2024 |
| Contact name |
Xin Yang |
| E-mail(s) |
xinyang2448@outlook.com
|
| Organization name |
Columbia University
|
| Department |
Institute for Cancer Genetics
|
| Lab |
Wei Gu
|
| Street address |
1130 Saint Nicholas Ave, ICRC building
|
| City |
New York |
| ZIP/Postal code |
10032 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA506256 |
| SRA |
SRP169950 |
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