Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I

Academic Article

Abstract

  • Ribosome biogenesis is essential for cell growth and proliferation and is commonly elevated in cancer. Accordingly, numerous oncogene and tumor suppressor signaling pathways target rRNA synthesis. In breast cancer, non-canonical Wnt signaling by Wnt5a has been reported to antagonize tumor growth. Here, we show that Wnt5a rapidly represses rDNA gene transcription in breast cancer cells and generates a chromatin state with reduced transcription of rDNA by RNA polymerase I (Pol I). These effects were specifically dependent on Dishevelled1 (DVL1), which accumulates in nucleolar organizer regions (NORs) and binds to rDNA regions of the chromosome. Upon DVL1 binding, the Pol I transcription activator and deacetylase Sirtuin 7 (SIRT7) releases from rDNA loci, concomitant with disassembly of Pol I transcription machinery at the rDNA promoter. These findings reveal that Wnt5a signals through DVL1 to suppress rRNA transcription. This provides a novel mechanism for how Wnt5a exerts tumor suppressive effects and why disruption of Wnt5a signaling enhances mammary tumor growth in vivo.
  • Published In

  • PLoS Genetics  Journal
  • Digital Object Identifier (doi)

    Author List

  • Dass RA; Sarshad AA; Carson BB; Feenstra JM; Kaur A; Obrdlik A; Parks MM; Prakash V; Love DK; Pietras K
  • Volume

  • 12
  • Issue

  • 8