Selective inhibition of ADAR2-catalyzed editing of the serotonin 2c receptor pre-mRNA by a helix-threading peptide

Nicole T. Schirle; Rena A. Goodman; Malathy Krishnamurthy; Peter A. Beal

doi:10.1039/c0ob00309c

Selective inhibition of ADAR2-catalyzed editing of the serotonin 2c receptor pre-mRNA by a helix-threading peptide

Nicole T. Schirle, Rena A. Goodman, Malathy Krishnamurthy, Peter A. Beal

Chemistry

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

RNA editing by adenosine deamination is a form of epigenetic control of gene expression wherein the ADAR enzymes convert adenosine to inosine in RNA often changing the meaning of codons. The pre-mRNA for the 2c subtype of serotonin receptor (5-HT2cR) is shown here to support small molecule binding near known editing sites. Furthermore, a helix-threading peptide binds this site and inhibits the in vitro reaction of ADAR2 in an RNA-substrate selective manner. This is the first example of substrate-selective inhibition of editing by an RNA-binding small molecule and sets the stage for the development of new reagents capable of controlling gene function through manipulation of mRNA editing.

Original language	English (US)
Pages (from-to)	4898-4904
Number of pages	7
Journal	Organic and Biomolecular Chemistry
Volume	8
Issue number	21
DOIs	https://doi.org/10.1039/c0ob00309c
State	Published - Nov 7 2010

ASJC Scopus subject areas

Physical and Theoretical Chemistry
Organic Chemistry
Biochemistry

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AU - Beal, Peter A.

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AB - RNA editing by adenosine deamination is a form of epigenetic control of gene expression wherein the ADAR enzymes convert adenosine to inosine in RNA often changing the meaning of codons. The pre-mRNA for the 2c subtype of serotonin receptor (5-HT2cR) is shown here to support small molecule binding near known editing sites. Furthermore, a helix-threading peptide binds this site and inhibits the in vitro reaction of ADAR2 in an RNA-substrate selective manner. This is the first example of substrate-selective inhibition of editing by an RNA-binding small molecule and sets the stage for the development of new reagents capable of controlling gene function through manipulation of mRNA editing.

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Selective inhibition of ADAR2-catalyzed editing of the serotonin 2c receptor pre-mRNA by a helix-threading peptide

Abstract

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