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p73 expression is regulated by ribosomal protein RPL26 through mRNA translation and protein stability

Min Zhang1,2, Jin Zhang2, Wensheng Yan2

  • 1College of Life Sciences and Technology, Huazhong Agricultural University, Wuhan, China.

Oncotarget
|November 9, 2016
PubMed

Insights

Ribosomal protein 26 (RPL26) regulates p73, a tumor suppressor, through both protein stability and mRNA translation. This discovery reveals new mechanisms controlling p73 expression and cell growth.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Tumor Suppressor Gene Regulation

Background:

  • The p73 protein, a member of the p53 family, functions as a tumor suppressor.
  • p73 expression is known to be regulated by transcriptional control, mRNA stability, and protein stability.
  • The role of mRNA translation in regulating p73 expression remained unexplored.

Purpose of the Study:

  • To investigate whether ribosomal protein 26 (RPL26) influences p73 expression.
  • To determine if RPL26 regulates p73 expression through mRNA translation.
  • To elucidate the mechanisms by which RPL26 controls p73 protein stability and mRNA translation.

Main Methods:

  • CRISPR-cas9 technology was used to generate MDM2-knockout cell lines.
  • Analysis of p73 protein half-life in the presence and absence of MDM2.
  • Assessment of polysome assembly and de novo protein synthesis of p73.
  • RNA immunoprecipitation (RIP) assays to study RPL26 binding to the p73 3' untranslated region (3'UTR).
  • Examination of RPL26 interaction with eIF4E and its effect on p73 mRNA translation.
  • Cell growth assays following RPL26 knockdown or overexpression.

Main Results:

  • RPL26 regulates p73 expression via both protein stability and mRNA translation.
  • In MDM2-knockout cells, RPL26 still influenced p73 expression, indicating multiple regulatory mechanisms.
  • RPL26 is essential for efficient polysome loading onto p73 mRNA and for de novo p73 protein synthesis.
  • RPL26 directly binds to the p73 3'UTR and enhances the association of eIF4E with p73 mRNA, boosting translation.
  • Knockdown of RPL26 promoted cell growth, while its overexpression inhibited growth in a TAp73-dependent manner.

Conclusions:

  • RPL26 acts as a critical regulator of p73 expression through distinct mechanisms.
  • RPL26 controls p73 protein stability, partly independent of MDM2.
  • RPL26 enhances p73 mRNA translation by facilitating cap-dependent initiation.
  • RPL26 plays a significant role in regulating cell growth through TAp73 modulation.
Keywords:
MDM2RPL26eIF4Ep73protein stability

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