Abstract
The tumor suppressor p53 triggers cell death by apoptosis in response to cellular stress. p53 is regulated at the protein level by various posttranslational modifications, such as phosphorylation and acetylation. However, recent studies have revealed a critical regulation of p53 at the RNA level. A natural antisense gene, designated Wrap53, is localized in a head-to-head fashion with p53 on human chromosome 17p13. Wrap53 mRNA positively regulates steady-state levels of p53 mRNA and p53 protein by targeting the 5′ untranslated region of p53 mRNA. Knockdown of Wrap53 by siRNA results in a significant decrease in p53 mRNA and suppression of p53 induction upon DNA damage, whereas overexpression of Wrap53 transcripts containing the antisense overlap region enhances p53 mRNA and protein levels and sensitizes cells to p53-dependent apoptosis. Antisense transcription, which occurs widely in mammalian genomes, is thought to play an important role in regulation of gene expression. Wrap53 antisense RNA is a novel mechanism for controlling p53 activity and an interesting example of antisense-mediated gene regulation in human cells.
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Acknowledgements
We thank the Swedish Cancer Society (Cancerfonden), the Swedish Childhood Cancer Society (Barncancerfonden), and the King Gustaf V Jubilee Fund for generous financial support.
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Farnebo, M., Wiman, K.G. (2010). Antisense RNA-Mediated Regulation of the p53 Tumor Suppressor. In: Erdmann, V., Barciszewski, J. (eds) RNA Technologies and Their Applications. RNA Technologies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-12168-5_12
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DOI: https://doi.org/10.1007/978-3-642-12168-5_12
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