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Annexin A2 and PSF proteins interact with p53 IRES and regulate translation of p53 mRNA

Arandkar Sharathchandra1, Ridhima Lal, Debjit Khan

  • 1Department of Microbiology and Cell Biology; Indian Institute of Science; Bangalore, India.

RNA Biology
|November 8, 2012
PubMed

Insights

Researchers identified Annexin A2 and PSF/SFPQ as new protein factors that regulate p53 mRNA translation via Internal Ribosome Entry Sites (IRES). These factors influence the production of both full-length p53 (FL-p53) and its truncated isoform, ΔN-p53.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Cancer Research

Background:

  • p53 mRNA produces two isoforms: full-length p53 (FL-p53) and a truncated form, ΔN-p53.
  • Internal Ribosome Entry Site (IRES) elements regulate the translation of both p53 isoforms in a cell-cycle-dependent manner.
  • p53 IRES function is sensitive to RNA structure and RNA-protein interactions.

Purpose of the Study:

  • Identify novel RNA-binding proteins that act as IRES trans-acting factors (ITAFs) for p53 IRES elements.
  • Investigate the role of Annexin A2 and PTB associated Splicing Factor (PSF/SFPQ) in regulating p53 isoform synthesis.

Main Methods:

  • RNA affinity assays to identify proteins binding to p53 IRES.
  • In vitro binding assays with purified Annexin A2 and PSF proteins.
  • Immunoprecipitation and knockdown experiments in cells.
  • Analysis of p53 isoform levels.

Main Results:

  • Annexin A2 and PSF/SFPQ were identified as novel ITAFs that specifically bind to p53 IRES elements.
  • Annexin A2 binding to p53 IRES is enhanced by calcium ions.
  • Knockdown of Annexin A2 or PSF/SFPQ reduced p53 IRES activity and the levels of both p53 isoforms.
  • The interaction between Annexin A2, PSF/SFPQ, and PTB is crucial for p53 IRES function.

Conclusions:

  • Annexin A2 and PSF/SFPQ are key regulators of p53 mRNA translation through IRES-mediated mechanisms.
  • These ITAFs influence the synthesis of both FL-p53 and ΔN-p53 isoforms.
  • The interplay of these ITAFs is critical for controlling p53 isoform production and function.
Keywords:
IRESIRES trans-acting factorsPSFinternal initiation of translation Annexin A2p53mRNA

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