5'-3'-UTR interactions regulate p53 mRNA translation and provide a target for modulating p53 induction after DNA damage.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chen, J; Kastan, MB

Published Date

  • October 1, 2010

Published In

Volume / Issue

  • 24 / 19

Start / End Page

  • 2146 - 2156

PubMed ID

  • 20837656

Pubmed Central ID

  • 20837656

Electronic International Standard Serial Number (EISSN)

  • 1549-5477

Digital Object Identifier (DOI)

  • 10.1101/gad.1968910

Language

  • eng

Conference Location

  • United States