Identification of Peptides with ELAV-like mRNA-Stabilizing Effect: An Integrated In Vitro/In Silico Approach

Authors

  • Marialaura Amadio,

    1. Pharmacology Section, Department of Drug Sciences, University of Pavia, Pavia, Italy
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    • These authors equally contributed to this work.
  • Alessia Pascale,

    1. Pharmacology Section, Department of Drug Sciences, University of Pavia, Pavia, Italy
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    • These authors equally contributed to this work.
  • Stefano Govoni,

    1. Pharmacology Section, Department of Drug Sciences, University of Pavia, Pavia, Italy
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  • Erik Laurini,

    1. Molecular Simulation Engineering (MOSE) Laboratory, Department of Industrial Engineering and Information Technology, University of Trieste, Trieste, Italy
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  • Sabrina Pricl,

    Corresponding author
    1. Molecular Simulation Engineering (MOSE) Laboratory, Department of Industrial Engineering and Information Technology, University of Trieste, Trieste, Italy
    • Pharmacology Section, Department of Drug Sciences, University of Pavia, Pavia, Italy
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  • Raffaella Gaggeri,

    1. Medicinal Chemistry and Pharmaceutical Technology Section, Department of Drug Sciences, University of Pavia, Pavia, Italy
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  • Daniela Rossi,

    1. Medicinal Chemistry and Pharmaceutical Technology Section, Department of Drug Sciences, University of Pavia, Pavia, Italy
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  • Simona Collina

    Corresponding author
    1. Medicinal Chemistry and Pharmaceutical Technology Section, Department of Drug Sciences, University of Pavia, Pavia, Italy
    • Pharmacology Section, Department of Drug Sciences, University of Pavia, Pavia, Italy
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Corresponding authors: Simona Collina, simona.collina@unipv.it; Sabrina Pricl, sabrina.pricl@di3.units.it

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.

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