5＇–3＇-UTR interactions regulate p53 mRNA translation and provide a target for modulating p53 induction after DNA damage
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Jing Chen and Michael B. Kastan
- چاپ و سال / کشور: 2010
Description
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 59- and 39-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 59–39-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.
GENES & DEVELOPMENT 24:2146–2156 2010 by Cold Spring Harbor Laboratory Press ISSN 0890-9369/10; www.genesdev.org Received July 12, 2010; revised version accepted August 12, 2010.
