Get access

Dicer Nuclease-Promoted Production of Let7a-1 MicroRNA Is Enhanced in the Presence of Tryptophan-Containing Amphiphilic Peptides

Authors

  • Dr. Soonsil Hyun,

    1. Department of Chemistry and Education, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742 (Korea)
    Search for more papers by this author
  • Areum Han,

    1. Department of Chemistry and Education, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742 (Korea)
    Search for more papers by this author
  • Myung Hyun Jo,

    1. Department of Physics and Astronomy, Department of Biophysics and Chemical Biology, and National Center for Creative Research Initiatives, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742 (Korea)
    Search for more papers by this author
  • Prof. Dr. Sungchul Hohng,

    1. Department of Physics and Astronomy, Department of Biophysics and Chemical Biology, and National Center for Creative Research Initiatives, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742 (Korea)
    Search for more papers by this author
  • Prof. Dr. Jaehoon Yu

    Corresponding author
    1. Department of Chemistry and Education, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742 (Korea)
    • Department of Chemistry and Education, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742 (Korea)===

    Search for more papers by this author

Abstract

A library of Trp-containing amphiphilic peptides was synthesized and screened for the ability to bind to pre-miRNA targets. Two members of this family, peptides Ac-WKKLLKWLKKLLKLAG-NH2 (2 b) and Ac-WKKLLKWLKKLLDabLAG-NH2 (4 b) were found to have nanomolar binding affinities to pre-let7a-1. Peptides 2 b and 4 b caused an increase in the in vitro Dicer cleavage of pre-let7a-1. This observation was confirmed by a cell-based assay, the results of which show an up to 50 % increase in Dicer activity. Enhanced expression of let7a-1 promoted by the peptides results in specific reductions of target mRNAs. The results of a microarray study show that lower amount of fluctuating genes are generated in the presence of 2 b or 4 b, relative to that from exogenous delivery of let7a-1. Because peptides 2 b and 4 b promote enhanced formation of mature let7a-1 only at the endogenous miRNA level, this specifically controls genes related to let7a-1.

Ancillary