Abstract |
The mechanisms involved in the p53-dependent control of gene expression following DNA damage have not been completely elucidated. Here, we show that the p53 C terminus associates with factors that are required for the ultraviolet (UV)-induced inhibition of the mRNA 3' cleavage step of the polyadenylation reaction, such as the tumor suppressor BARD1 and the 3' processing factor cleavage-stimulation factor 1 (CstF1). We found that p53 can coexist in complexes with CstF and BARD1 in extracts of UV-treated cells, suggesting a role for p53 in mRNA 3' cleavage following DNA damage. Consistent with this, we found that p53 inhibits 3' cleavage in vitro and that there is a reverse correlation between the levels of p53 expression and the levels of mRNA 3' cleavage under different cellular conditions. Supporting these results, a tumor-associated mutation in p53 not only decreases the interaction with BARD1 and CstF, but also decreases the UV-induced inhibition of 3' processing, all of which is restored by wild-type-p53 expression. We also found that p53 expression levels affect the polyadenylation levels of housekeeping genes, but not of p21 and c-fos genes, which are involved in the DNA damage response (DDR). Here, we identify a novel 3' RNA processing inhibitory function of p53, adding a new level of complexity to the DDR by linking RNA processing to the p53 network.
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Authors | F I Nazeer, E Devany, S Mohammed, D Fonseca, B Akukwe, C Taveras, F E Kleiman |
Journal | Oncogene
(Oncogene)
Vol. 30
Issue 27
Pg. 3073-83
(Jul 07 2011)
ISSN: 1476-5594 [Electronic] England |
PMID | 21383700
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cleavage Stimulation Factor
- RNA, Messenger
- Tumor Suppressor Protein p53
- Tumor Suppressor Proteins
- BARD1 protein, human
- Ubiquitin-Protein Ligases
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Topics |
- Cell Line
- Cleavage Stimulation Factor
(physiology)
- Humans
- RNA Processing, Post-Transcriptional
(physiology)
- RNA, Messenger
(genetics)
- Tumor Suppressor Protein p53
(physiology)
- Tumor Suppressor Proteins
(physiology)
- Ubiquitin-Protein Ligases
(physiology)
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