The RNA helicase DHX9 is an ATP-dependent DExH box helicase that can unwind DNA
and RNA. Much evidence has implicated DHX9 at multiple levels of gene expression regulation
ranging from genome stability and replication, to transcriptional control and translation regulation. Its
association with the EWS-FLI1 fusion product, as well as the finding that its suppression can be
synthetic lethal with the BCL-2 family inhibitor ABT-737 indicates a potential role in tumor
maintenance. Hence, to identify small molecules that could interfere with its activity, we developed a
homogenous RNA-dependent ATPase assay. We show that aurintricarboxylic acid, a promiscuous
protein-nucleic acid inhibitor prevents DHX9-mediated hydrolysis demonstrating that the assay is also capable of
detecting compounds that impinge on DHX9:RNA association.
Keywords: ATPase assay, ATA, aurintricarboxylic acid, DHX9, HTS, RNA binding, RNA helicase.
Rights & PermissionsPrintExport