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Molecular Glue for RNA: Regulating RNA Structure and Function through Synthetic RNA Binding Molecules
Author(s) -
Dohno Chikara,
Nakatani Kazuhiko
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.201900223
Subject(s) - rna , chemistry , riboswitch , nucleic acid structure , computational biology , function (biology) , molecule , non coding rna , biophysics , microbiology and biotechnology , biochemistry , biology , gene , organic chemistry
We introduce the concept of molecular glues for RNA, in which specific RNA‐binding small molecules induce designed structural changes in target functional RNAs, resulting in modulation of the functions. ( Z )‐NCTS is an RNA‐mismatch‐binding small molecule that recognizes 5′‐r(XGG)‐3′/5′‐r(XGG)‐3′ sequences (X=U or A) and acts as a molecular glue for RNA. The binding of ( Z )‐NCTS brings two distinct 5′‐r(XGG)‐3′ domains into contact with each other, and this can result in higher‐order structural changes of target RNAs. We applied ( Z )‐NCTS to induce the formation of a proposed tertiary structure of a ribozyme together with activation of RNA‐cleaving ability. The concept of a molecular glue could inspire new small‐molecule‐based strategies for regulating biological functions: a synthetic small molecule targeting functional RNAs could regulate the RNA structure and function.