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Exploring structural determinants and the role of nucleolin in formation of the long-range interactions between

Agnieszka Kiliszek1, Wojciech Rypniewski1, Leszek Błaszczyk2

  • 1Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704 Poznań, Poland.

RNA (New York, N.Y.)
|January 18, 2023
PubMed

Insights

This study reveals how p53 mRNA uses a bulge motif and nucleolin to regulate p53 protein translation under stress. Nucleolin acts as an RNA chaperone, facilitating crucial RNA-RNA interactions for cellular homeostasis.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Gene Regulation

Background:

  • p53 protein is vital for cellular homeostasis and antiproliferative responses to stress.
  • While post-translational modifications are key, mRNA-level regulation of p53 expression is increasingly recognized.
  • Understanding mRNA structure and interactions is crucial for deciphering p53 regulation.

Purpose of the Study:

  • To investigate structural determinants of long-range RNA-RNA interactions in p53 mRNA.
  • To elucidate the role of the 8-nt bulge motif in p53 mRNA structure and function.
  • To determine the involvement of nucleolin in regulating p53 mRNA translation.

Main Methods:

  • Analysis of structural determinants in p53 mRNA.
  • Investigating RNA-RNA interactions within p53 mRNA using mutational analysis.
  • Assessing the RNA chaperone activity of nucleolin on p53 mRNA.
  • Studying the impact of mutations on base-pairing and translation regulation.

Main Results:

  • An 8-nt bulge motif in p53 mRNA is critical for base-pairing between 5' and 3' untranslated regions.
  • Nucleolin exhibits RNA chaperone activity, promoting these long-range RNA-RNA interactions.
  • Mutations in the bulge motif disrupt pairing, while compensatory mutations restore it.
  • All four RNA recognition motifs of nucleolin are essential for its chaperone activity.

Conclusions:

  • The 8-nt bulge motif and nucleolin are critical factors in intramolecular RNA-RNA recognition within p53 mRNA.
  • These findings reveal a unique mechanism for stress-dependent regulation of p53 protein translation at the mRNA level.
  • This study enhances understanding of how p53 mRNA structure influences protein output during cellular stress.
Keywords:
RNA chaperone activityRNA structureRNA–RNA interactionsnucleolinp53 mRNAp53 protein

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