RNA-binding protein RBM24 regulates p63 expression via mRNA stability

Mol Cancer Res. 2014 Mar;12(3):359-69. doi: 10.1158/1541-7786.MCR-13-0526. Epub 2013 Dec 27.

Abstract

p63, a p53 family member, plays pivotal roles in epidermal development, aging, and tumorigenesis. Thus, understanding how p63 expression is controlled has biological and clinical importance. RBM24 is an RNA-binding protein and shares a high sequence similarity with RBM38, a critical regulator of p63. In this study, we investigated whether RBM24 is capable of regulating p63 expression. Indeed, we found that ectopic expression of RBM24 decreased, whereas knockdown of RBM24 increased, the levels of p63 transcript and protein. To explore the underlying mechanism, we found that RBM24 was able to bind to multiple regions in the p63 3' untranslated region and, subsequently, destabilize p63 transcript. Furthermore, we showed that the 3' untranslated region in p63 transcript and the RNA-binding domain in RBM24 were required for RBM24 to bind p63 transcript and consequently, inhibit p63 expression. Taken together, our data provide evidence that RBM24 is a novel regulator of p63 via mRNA stability.

Implications: Our study suggests that p63 is regulated by RBM24 via mRNA stability, which gives an insight into understanding how posttranscriptional regulatory mechanisms contribute to p63 expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions
  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / physiology
  • Gene Expression
  • Gene Knockdown Techniques
  • HCT116 Cells
  • Humans
  • MCF-7 Cells
  • Mice
  • Molecular Sequence Data
  • Plasmids / genetics
  • RNA Stability*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics

Substances

  • 3' Untranslated Regions
  • RBM24 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Rbm24 protein, mouse
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins