Selective inhibition of ADAR2-catalyzed editing of the serotonin 2c receptor pre-mRNA by a helix-threading peptide.
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.
Schirle
Nicole T
NT
Department of Chemistry, University of California, Davis, CA 95616, USA.
Goodman
Rena A
RA
Krishnamurthy
Malathy
M
Beal
Peter A
PA
D000243:Adenosine Deaminase / Q000378:metabolism*; D058892:Adenosine Deaminase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D017393:RNA Editing / Q000187:drug effects*; D012322:RNA Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*
D058892:Adenosine Deaminase Inhibitors; D010455:Peptides; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D044405:Receptor, Serotonin, 5-HT2C; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase