Identification of peptides with ELAV-like mRNA-stabilizing effect: an integrated in vitro/in silico approach

Chem Biol Drug Des. 2013 Jun;81(6):707-14. doi: 10.1111/cbdd.12117. Epub 2013 Apr 11.

Abstract

Embryonic lethal abnormal vision (ELAV) proteins are RNA-binding proteins that bind specific adenine and uridine-rich elements mainly located in the 3'-untranslated region of target mRNAs, preventing their otherwise rapid degradation and thus increasing gene expression. Starting from our previous discovery and applying an integrated in vitro/in silico approach, herein we report a deeper understanding of the mRNA-stabilizing activity of four peptides derived from the ELAV proteins structure. The stabilizing effect on the VEGF transcript (mRNAVEGF ) exerted by each peptide, tested individually, was initially evaluated, and no effects were evidenced. Hence, the biological effects of all peptides couples were investigated. Interestingly, in accordance with preliminary molecular dynamics results, only one of all possible peptide couples resulted highly effective in stabilizing mRNAVEGF . These two peptides were thus identified as valuable starting point for designing small molecules with ELAV-mimicking properties.

MeSH terms

  • Cell Line, Tumor
  • ELAV Proteins / chemistry*
  • ELAV Proteins / genetics
  • ELAV Proteins / metabolism
  • Humans
  • Molecular Dynamics Simulation
  • Peptides / chemical synthesis
  • Peptides / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Stability
  • RNA, Messenger / metabolism*
  • Thermodynamics
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • ELAV Proteins
  • Peptides
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A