Dicer nuclease-promoted production of Let7a-1 microRNA is enhanced in the presence of tryptophan-containing amphiphilic peptides.

Soonsil Hyun, Areum Han, Myung Hyun Jo, Sungchul Hohng, Jaehoon Yu

Index: ChemBioChem. 15(11) , 1651-9, (2014)

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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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.