MDM2 expression is repressed by the RNA-binding protein RNPC1 via mRNA stability

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The RNA-binding protein (RBP) RNPC1 is a target of the p53 family and forms a feedback regulatory loop with the p53 family proteins. The murine double minute-2 (MDM2) oncogene, a key negative regulator of p53, has a critical role in a variety of fundamental cellular processes. MDM2 expression is found to be regulated via gene amplification, transcription, protein translation and protein stability. In the current study, we reported a novel regulation of MDM2 by RNPC1 via mRNA stability. Specifically, we found that overexpression of RNPC1 decreases, whereas knockdown or knockout of RNPC1 increases, the level of MDM2 transcript and protein independent of p53. To uncover the underlying mechanism, we found that RNPC1 is able to destabilize the MDM2 transcript via binding to multiple AU-/U-rich elements in MDM2 3′untranslated region (3′UTR). Consistent with this, we showed that RNPC1 inhibits expression of exogenous MDM2 from an expression vector as long as the vector contains an AU-/U-rich element from MDM2 3′UTR. Finally, we showed that the RNA-binding activity of RNPC1 is required for binding to MDM2 transcript and consequently, for inhibiting MDM2 expression. Together, we uncover a novel regulation of MDM2 by the RBP RNPC1 via mRNA stability.

Original languageEnglish (US)
Pages (from-to)2169-2178
Number of pages10
JournalOncogene
Volume32
Issue number17
DOIs
StatePublished - 2013

Fingerprint

AU Rich Elements
RNA-Binding Proteins
RNA Stability
Proto-Oncogene Proteins c-mdm2
Gene Amplification
Protein Stability
Protein Biosynthesis
Oncogenes
RNA
Proteins

Keywords

  • MDM2
  • mRNA stability
  • RNA-binding proteins
  • RNPC1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

MDM2 expression is repressed by the RNA-binding protein RNPC1 via mRNA stability. / Xu, E.; Zhang, Jin; Chen, Xinbin.

In: Oncogene, Vol. 32, No. 17, 2013, p. 2169-2178.

Research output: Contribution to journalArticle

@article{5f8aef8e73de4f90846370f133b974b7,
title = "MDM2 expression is repressed by the RNA-binding protein RNPC1 via mRNA stability",
abstract = "The RNA-binding protein (RBP) RNPC1 is a target of the p53 family and forms a feedback regulatory loop with the p53 family proteins. The murine double minute-2 (MDM2) oncogene, a key negative regulator of p53, has a critical role in a variety of fundamental cellular processes. MDM2 expression is found to be regulated via gene amplification, transcription, protein translation and protein stability. In the current study, we reported a novel regulation of MDM2 by RNPC1 via mRNA stability. Specifically, we found that overexpression of RNPC1 decreases, whereas knockdown or knockout of RNPC1 increases, the level of MDM2 transcript and protein independent of p53. To uncover the underlying mechanism, we found that RNPC1 is able to destabilize the MDM2 transcript via binding to multiple AU-/U-rich elements in MDM2 3′untranslated region (3′UTR). Consistent with this, we showed that RNPC1 inhibits expression of exogenous MDM2 from an expression vector as long as the vector contains an AU-/U-rich element from MDM2 3′UTR. Finally, we showed that the RNA-binding activity of RNPC1 is required for binding to MDM2 transcript and consequently, for inhibiting MDM2 expression. Together, we uncover a novel regulation of MDM2 by the RBP RNPC1 via mRNA stability.",
keywords = "MDM2, mRNA stability, RNA-binding proteins, RNPC1",
author = "E. Xu and Jin Zhang and Xinbin Chen",
year = "2013",
doi = "10.1038/onc.2012.238",
language = "English (US)",
volume = "32",
pages = "2169--2178",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "17",

}

TY - JOUR

T1 - MDM2 expression is repressed by the RNA-binding protein RNPC1 via mRNA stability

AU - Xu, E.

AU - Zhang, Jin

AU - Chen, Xinbin

PY - 2013

Y1 - 2013

N2 - The RNA-binding protein (RBP) RNPC1 is a target of the p53 family and forms a feedback regulatory loop with the p53 family proteins. The murine double minute-2 (MDM2) oncogene, a key negative regulator of p53, has a critical role in a variety of fundamental cellular processes. MDM2 expression is found to be regulated via gene amplification, transcription, protein translation and protein stability. In the current study, we reported a novel regulation of MDM2 by RNPC1 via mRNA stability. Specifically, we found that overexpression of RNPC1 decreases, whereas knockdown or knockout of RNPC1 increases, the level of MDM2 transcript and protein independent of p53. To uncover the underlying mechanism, we found that RNPC1 is able to destabilize the MDM2 transcript via binding to multiple AU-/U-rich elements in MDM2 3′untranslated region (3′UTR). Consistent with this, we showed that RNPC1 inhibits expression of exogenous MDM2 from an expression vector as long as the vector contains an AU-/U-rich element from MDM2 3′UTR. Finally, we showed that the RNA-binding activity of RNPC1 is required for binding to MDM2 transcript and consequently, for inhibiting MDM2 expression. Together, we uncover a novel regulation of MDM2 by the RBP RNPC1 via mRNA stability.

AB - The RNA-binding protein (RBP) RNPC1 is a target of the p53 family and forms a feedback regulatory loop with the p53 family proteins. The murine double minute-2 (MDM2) oncogene, a key negative regulator of p53, has a critical role in a variety of fundamental cellular processes. MDM2 expression is found to be regulated via gene amplification, transcription, protein translation and protein stability. In the current study, we reported a novel regulation of MDM2 by RNPC1 via mRNA stability. Specifically, we found that overexpression of RNPC1 decreases, whereas knockdown or knockout of RNPC1 increases, the level of MDM2 transcript and protein independent of p53. To uncover the underlying mechanism, we found that RNPC1 is able to destabilize the MDM2 transcript via binding to multiple AU-/U-rich elements in MDM2 3′untranslated region (3′UTR). Consistent with this, we showed that RNPC1 inhibits expression of exogenous MDM2 from an expression vector as long as the vector contains an AU-/U-rich element from MDM2 3′UTR. Finally, we showed that the RNA-binding activity of RNPC1 is required for binding to MDM2 transcript and consequently, for inhibiting MDM2 expression. Together, we uncover a novel regulation of MDM2 by the RBP RNPC1 via mRNA stability.

KW - MDM2

KW - mRNA stability

KW - RNA-binding proteins

KW - RNPC1

UR - http://www.scopus.com/inward/record.url?scp=84876927156&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876927156&partnerID=8YFLogxK

U2 - 10.1038/onc.2012.238

DO - 10.1038/onc.2012.238

M3 - Article

VL - 32

SP - 2169

EP - 2178

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 17

ER -