Dicer Nuclease‐Promoted Production of Let7a‐1 MicroRNA Is Enhanced in the Presence of Tryptophan‐Containing Amphiphilic Peptides. Issue 11 (2nd July 2014)

• Record Type: Journal Article
• Authors: Hyun, Soonsil; Han, Areum; Jo, Myung Hyun; Hohng, Sungchul; Yu, Jaehoon
• Is Part Of: Chembiochem. Volume 15:Issue 11(2014)
• Page Start: 1651
• Page End: 1659
• Publication Date: 2014-07-02
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201402126
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 (<bold>2 b</bold>) and Ac‐WKKLLKWLKKLLDabLAG‐NH₂ (<bold>4 b</bold>) were found to have nanomolar binding affinities to pre‐let7a‐1. Peptides <bold>2 b</bold> and <bold>4 b</bold> 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 <bold>2 b</bold> or <bold>4 b</bold>, relative to that from exogenous delivery of let7a‐1. Because peptides <bold>2 b</bold> and <bold>4 b</bold> promote enhanced formation of mature let7a‐1 only at the endogenous miRNA level, this specifically controls genes related to let7a‐1.</p> </abstract>