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

Fingerprint

Nonsense Mediated mRNA Decay
Cyclin-Dependent Kinases
Open Reading Frames
Messenger RNA
RNA Cap-Binding Proteins
Protein Biosynthesis
Microarray Analysis
Quality Control
Down-Regulation
Microarrays
Quality control

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

@article{f86c376831c74d5d96088a7c4bf82e5c,
title = "The upstream open reading frame of cyclin-dependent kinase inhibitor 1A mRNA negatively regulates translation of the downstream main open reading frame",
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.",
keywords = "CBP20, CBP80, CDKN1A/p21/WAF1, NMD, UORF",
author = "Kim, {Kyoung Mi} and Hana Cho and Kim, {Yoon Ki}",
year = "2012",
month = "8",
day = "3",
doi = "10.1016/j.bbrc.2012.06.135",
language = "English",
volume = "424",
pages = "469--475",
journal = "The BMJ",
issn = "0730-6512",
publisher = "Kluwer Academic Publishers",
number = "3",

}

TY - JOUR

T1 - The upstream open reading frame of cyclin-dependent kinase inhibitor 1A mRNA negatively regulates translation of the downstream main open reading frame

AU - Kim, Kyoung Mi

AU - Cho, Hana

AU - Kim, Yoon Ki

PY - 2012/8/3

Y1 - 2012/8/3

N2 - 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.

AB - 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.

KW - CBP20

KW - CBP80

KW - CDKN1A/p21/WAF1

KW - NMD

KW - UORF

UR - http://www.scopus.com/inward/record.url?scp=84864751261&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864751261&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2012.06.135

DO - 10.1016/j.bbrc.2012.06.135

M3 - Article

C2 - 22771799

AN - SCOPUS:84864751261

VL - 424

SP - 469

EP - 475

JO - The BMJ

JF - The BMJ

SN - 0730-6512

IS - 3

ER -