The upstream open reading frame of cyclin-dependent kinase inhibitor 1A mRNA negatively regulates translation of the downstream main open reading frame

Kyoung Mi Kim, Hana Cho, Yoon Ki Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The first round of translation occurs on mRNAs bound by nuclear cap-binding complex (CBC), which is composed of nuclear cap-binding protein 80 and 20 (CBP80/20). During this round of translation, aberrant mRNAs are recognized and downregulated in abundance by nonsense-mediated mRNA decay (NMD), which is one of the mRNA quality control mechanisms. Here, our microarray analysis reveals that the level of cyclin-dependent kinase inhibitor 1A (CDKN1A; also known as Waf1/p21) mRNAs increases in cells depleted of cellular NMD factors. Intriguingly, CDKN1A mRNA contains an upstream open reading frame (uORF), which is a NMD-inducing feature. Using chimeric reporter constructs, we find that the uORF of CDKN1A mRNA negatively modulates translation of the main downstream ORF. These findings provide biological insights into the possible role of NMD in diverse biological pathways mediated by CDKN1A.

Original languageEnglish
Pages (from-to)469-475
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume424
Issue number3
DOIs
Publication statusPublished - 2012 Aug 3

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Keywords

  • CBP20
  • CBP80
  • CDKN1A/p21/WAF1
  • NMD
  • UORF

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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