p53 inhibits mRNA 3' processing through its interaction with the CstF/BARD1 complex.

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Nazeer FI,Devany E,Mohammed S,Fonseca D,Akukwe B,Taveras C,Kleiman FE

doi

10.1038/onc.2011.29

subject

Has Abstract

pub_date

2011-07-07 00:00:00

pages

3073-83

issue

27

eissn

0950-9232

issn

1476-5594

pii

onc201129

journal_volume

30

pub_type

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