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hnRNP H/F 与 G 四链体之间的相互作用对于维持 DNA 损伤过程中 p53 前体 mRNA 3'-末端加工和功能至关重要。

Essential role for the interaction between hnRNP H/F and a G quadruplex in maintaining p53 pre-mRNA 3'-end processing and function during DNA damage.

机构信息

INSERM U563, Institut Claudius Regaud, Toulouse, France.

出版信息

Genes Dev. 2011 Feb 1;25(3):220-5. doi: 10.1101/gad.607011.

DOI:10.1101/gad.607011
PMID:21289067
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3034896/
Abstract

Following DNA damage, mRNA 3'-end formation is inhibited, contributing to repression of mRNA synthesis. Here we investigated how DNA-damaged cells accomplish p53 mRNA 3'-end formation when normal mechanisms of pre-mRNA 3'-end processing regulation are inhibited. The underlying mechanism involves the interaction between a G-quadruplex structure located downstream from the p53 cleavage site and hnRNP H/F. Importantly, this interaction is critical for p53 expression and contributes to p53-mediated apoptosis. Our results uncover the existence of a specific rescue mechanism of 3'-end processing regulation allowing stress-induced p53 accumulation and function in apoptosis.

摘要

在 DNA 损伤后，mRNA 3'端的形成受到抑制，导致 mRNA 合成受到抑制。在这里，我们研究了在正常的前体 mRNA 3'端加工调控机制被抑制的情况下，DNA 损伤细胞如何完成 p53 mRNA 3'端的形成。其潜在的机制涉及位于 p53 切割位点下游的 G-四链体结构与 hnRNP H/F 之间的相互作用。重要的是，这种相互作用对于 p53 的表达至关重要，并有助于 p53 介导的细胞凋亡。我们的研究结果揭示了一种特定的 3'端加工调控的挽救机制的存在，该机制允许应激诱导的 p53 积累和在细胞凋亡中的功能。

相似文献

[1]
Essential role for the interaction between hnRNP H/F and a G quadruplex in maintaining p53 pre-mRNA 3'-end processing and function during DNA damage.

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[7]
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本文引用的文献

[1]
Nuclear deadenylation/polyadenylation factors regulate 3' processing in response to DNA damage.

EMBO J. 2010-4-8

[2]
Heterogeneous nuclear ribonucleoprotein H blocks MST2-mediated apoptosis in cancer cells by regulating A-Raf transcription.

Cancer Res. 2010-2-9

[3]
Molecular mechanisms of eukaryotic pre-mRNA 3' end processing regulation.

Nucleic Acids Res. 2009-12-30

[4]
The first 30 years of p53: growing ever more complex.

Nat Rev Cancer. 2009-10

[5]
Mechanism of the internal ribosome entry site-mediated translation of serine hydroxymethyltransferase 1.

J Biol Chem. 2009-11-6

[6]
G-quadruplex structures: in vivo evidence and function.

Trends Cell Biol. 2009-8

[7]
A physical and functional link between splicing factors promotes pre-mRNA 3' end processing.

Nucleic Acids Res. 2009-8

[8]
Modes of p53 regulation.

Cell. 2009-5-15

[9]
CPEB regulation of human cellular senescence, energy metabolism, and p53 mRNA translation.

Genes Dev. 2008-12-15

[10]
Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26.

Mol Cell. 2008-10-24

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