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

Research output: Contribution to journalArticle

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Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I. / Dass, Randall A.; Sarshad, Aishe A.; Carson, Brittany B.; Feenstra, Jennifer M.; Kaur, Amanpreet; Obrdlik, Ales; Parks, Matthew M.; Prakash, Varsha; Love, Damon K.; Pietras, Kristian; Serra, Rosa; Blanchard, Scott C.; Percipalle, Piergiorgio; Brown, Anthony M C; Vincent, C. Theresa.

In: PLoS Genetics, Vol. 12, No. 8, e1006217, 01.08.2016.

Research output: Contribution to journalArticle

Harvard

Dass, RA, Sarshad, AA, Carson, BB, Feenstra, JM, Kaur, A, Obrdlik, A, Parks, MM, Prakash, V, Love, DK, Pietras, K, Serra, R, Blanchard, SC, Percipalle, P, Brown, AMC & Vincent, CT 2016, 'Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I', PLoS Genetics, vol. 12, no. 8, e1006217. https://doi.org/10.1371/journal.pgen.1006217

APA

Dass, R. A., Sarshad, A. A., Carson, B. B., Feenstra, J. M., Kaur, A., Obrdlik, A., ... Vincent, C. T. (2016). Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I. PLoS Genetics, 12(8), [e1006217]. https://doi.org/10.1371/journal.pgen.1006217

CBE

Dass RA, Sarshad AA, Carson BB, Feenstra JM, Kaur A, Obrdlik A, Parks MM, Prakash V, Love DK, Pietras K, Serra R, Blanchard SC, Percipalle P, Brown AMC, Vincent CT. 2016. Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I. PLoS Genetics. 12(8). https://doi.org/10.1371/journal.pgen.1006217

MLA

Vancouver

Dass RA, Sarshad AA, Carson BB, Feenstra JM, Kaur A, Obrdlik A et al. Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I. PLoS Genetics. 2016 Aug 1;12(8). e1006217. https://doi.org/10.1371/journal.pgen.1006217

Author

Dass, Randall A. ; Sarshad, Aishe A. ; Carson, Brittany B. ; Feenstra, Jennifer M. ; Kaur, Amanpreet ; Obrdlik, Ales ; Parks, Matthew M. ; Prakash, Varsha ; Love, Damon K. ; Pietras, Kristian ; Serra, Rosa ; Blanchard, Scott C. ; Percipalle, Piergiorgio ; Brown, Anthony M C ; Vincent, C. Theresa. / Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I. In: PLoS Genetics. 2016 ; Vol. 12, No. 8.

RIS

TY - JOUR

T1 - Wnt5a Signals through DVL1 to Repress Ribosomal DNA Transcription by RNA Polymerase I

AU - Dass, Randall A.

AU - Sarshad, Aishe A.

AU - Carson, Brittany B.

AU - Feenstra, Jennifer M.

AU - Kaur, Amanpreet

AU - Obrdlik, Ales

AU - Parks, Matthew M.

AU - Prakash, Varsha

AU - Love, Damon K.

AU - Pietras, Kristian

AU - Serra, Rosa

AU - Blanchard, Scott C.

AU - Percipalle, Piergiorgio

AU - Brown, Anthony M C

AU - Vincent, C. Theresa

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84984914891&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1006217

DO - 10.1371/journal.pgen.1006217

M3 - Article

VL - 12

JO - PLoS Genetics

T2 - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7404

IS - 8

M1 - e1006217

ER -