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Putative Impact of RNA Editing on Drug Discovery
Author(s) -
Decher Niels,
Netter Michael F.,
Streit Anne K.
Publication year - 2013
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12045
Subject(s) - rna editing , rna , drug discovery , computational biology , biology , genome editing , mechanism (biology) , gene , genetics , bioinformatics , genome , philosophy , epistemology
Virtually all organisms use RNA editing as a powerful post‐transcriptional mechanism to recode genomic information and to increase functional protein diversity. The enzymatic editing of pre‐mRNA by ADARs and CDARs is known to change the functional properties of neuronal receptors and ion channels regulating cellular excitability. However, RNA editing is also an important mechanism for genes expressed outside the brain. The fact that RNA editing breaks the ‘one gene encodes one protein’ hypothesis is daunting for scientists and a probable drawback for drug development, as scientists might search for drugs targeting the ‘wrong’ protein. This possible difficulty for drug discovery and development became more evident from recent publications, describing that RNA editing events have profound impact on the pharmacology of some common drug targets. These recent studies highlight that RNA editing can cause massive discrepancies between the in vitro and in vivo pharmacology. Here, we review the putative impact of RNA editing on drug discovery, as RNA editing has to be considered before using high‐throughput screens, rational drug design or choosing the right model organism for target validation.