title: Dicer nuclease-promoted production of Let7a-1 microRNA is enhanced in the presence of tryptophan-containing amphiphilic peptides.
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.
authors.affiliation: Department of Chemistry and Education, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742 (Korea).
authors.forename: Soonsil
authors.initials: S
authors.lastname: Hyun
authors.forename: Areum
authors.initials: A
authors.lastname: Han
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Jo
authors.forename: Sungchul
authors.initials: S
authors.lastname: Hohng
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Yu
mesh_terms: D035683:MicroRNAs / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D043244:Ribonuclease III / Q000378:metabolism*; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D009842:Oligopeptides; D013501:Surface-Active Agents; D014364:Tryptophan; D043244:Ribonuclease III
keywords: Dicer nuclease; gene expression; let7a-1; microRNA; peptides