Disruption of pathways regulated by Integrator complex in Galloway-Mowat syndrome due to WDR73 mutations.

ABSTRACT: Several studies have reported WDR73 mutations to be causative of Galloway-Mowat syndrome, a rare disorder characterised by the association of neurological defects and renal-glomerular disease. In this study, we demonstrate interaction of WDR73 with the INTS9 and INTS11 components of Integrator, a large multiprotein complex with various roles in RNA metabolism and transcriptional control. We implicate WDR73 in two Integrator-regulated cellular pathways; namely, the processing of uridylate-rich small nuclear RNAs (UsnRNA), and mediating the transcriptional response to epidermal growth factor stimulation. We also show that WDR73 suppression leads to altered expression of genes encoding cell cycle regulatory proteins. Altogether, our results suggest that a range of cellular pathways are pertur

SUBMITTER: Tilley FC 

PROVIDER: S-EPMC7940485 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature