5′-3′-UTR interactions regulate p53 mRNA translation and provide a target for modulating p53 induction after DNA damage
Open accessAbstract
Optimal induction of p53 protein after DNA damage requires RPL26-mediated increases in p53 mRNA translation. We report here the existence of a dsRNA region containing complementary sequences of the 5′- and 3′-untranslated regions (UTRs) of human p53 mRNA that is critical for its translational regulation by RPL26. Mutating as few as 3 bases in either of the two complementary UTR sequences abrogates the ability of RPL26 to bind to p53 mRNA and stimulate p53 translation, while compensatory mutations restore this binding and regulation. Short, single-strand oligonucleotides that target this 5′–3′-UTR base-pairing region blunt the binding of RPL26 to p53 mRNA in cells and reduce p53 induction and p53-mediated cell death after several different types of DNA damage and cellular stress. The ability to reduce stress induction of p53 with oligonucleotides or other small molecules has numerous potential therapeutic uses.
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The 5′UTR and 3′UTR of p53 mRNA contain complementary regions that bind translation factor RPL26, which mediates translation enhancement in response to DNA damage.
“Although a 5′UTR and 3′UTR do not interact directly during translation, it has been demonstrated by means of p53 mRNA as an example that the 5′UTR and 3′UTR contain complementary regions that bind translation factor RPL26, which mediates translation enhancement in response to DNA damage [40].”
From Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA (2023) · cites this paper as [40]
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Effects of Combinations of Untranslated-Region Sequences on Translation of mRNA
Kirshina, A., Vasileva, O., Kunyk, D., Seregina, K., Muslimov, A., Ivanov, R., & Reshetnikov, V. (2023) · Biomolecules · doi:10.3390/biom13111677 · Cited by 26 · see citing works
- Authors
- Chen, J., & Kastan, M. B.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-09-13
- Volume
- 24
- Issue
- 19
- Pages
- 2146-2156
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2947767
- OpenAlex
- W2155766860
- Cited by
- 127
- References
- 11
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 6 · 2016: 11 · 2015: 10 · 2014: 11 · 2013: 14 · 2012: 13
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- St. Jude Children's Research Hospital
- American Lebanese Syrian Associated Charities
- National Institutes of Health
- National Cancer Institute (P30CA021765)
- National Institute of Environmental Health Sciences (R37ES005777)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- p53, mRNA translation, RPL26, double-stranded RNA, p53 activation, DNA damage response, translational regulation, cellular stress
- MeSH terms
- DNA Damage, Gene Expression Regulation, Humans, Oligonucleotides, Protein Binding, Ribosomal Proteins, RNA, Double-Stranded, RNA, Messenger, Stress, Physiological, Tumor Suppressor Protein p53, 5' Untranslated Regions, 3' Untranslated Regions
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