RNA Targets and Function of Topoisomerase 3ß in Reducing Stress in Neuronal Physiology

Topoisomerase 3ß (Top3ß) relaxes DNA and RNA and its dysregulation is implicated in various neurodevelopmental and cognitive disorders. We developed a novel protocol to isolate RNA targets of the topoisomerase without artificial cross-linking and used it to identify the RNA targets of Top3ß. Lack of the enzymatic activity of Top3ß affects gene expression of (pre)mRNAs with the characteristics described for the Top3ß targets and we found evidence that this might also apply to several neurological diseases and cancers with which human Top3ß was associated. Overall design: To test if the lack of the enzymatic activity of Top3ß stresses neurons, affecting the morphology of the neuromuscular junction (NMJ) in adult flies, and it causes premature aging and loss of coordinated movement.