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.
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。
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