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A Small Cyclic β‐Hairpin Peptide Mimics the Rbfox2 RNA Recognition Motif and Binds to the Precursor miRNA 20b
Author(s) -
Sun YiTing,
Shortridge Matthew D.,
Varani Gabriele
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800645
Subject(s) - rna recognition motif , rna , peptide , rna binding protein , chemistry , small hairpin rna , biochemistry , structural motif , stem loop , peptide sequence , cyclic peptide , microbiology and biotechnology , biology , gene
The RNA recognition motif (RRM), which is the most abundant RNA‐binding motif in eukaryotes, is a well‐structured domain of about 90 amino acids, yet the β2β3 hairpin, corresponding to strands 2 and 3 of the β‐sheet, and the intervening loop make essential interactions with RNA in many RRM complexes. A series of small cyclic peptide mimics of the β2β3 hairpin of Rbfox2 protein that recognize the terminal loop of precursor miR‐20b have been designed to investigate whether the full RNA‐binding protein can be mimicked with a minimal structurally preorganized peptide. Within a small library of seven cyclic peptides, a peptide with low‐micromolar affinity for the miR‐20b precursor was found. NMR spectroscopy titration data suggest that this peptide specifically targets the apical loop of pre‐miR‐20b. This work shows that it is possible to mimic RNA‐binding proteins with designed stable peptides, which provide a starting point for designing or evolving small peptide mimetics of RRM proteins.