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Promoter proximal pausing limits Yki-induced tumorous growth in Drosophila

Sanket Nagarkar, Ruchi Wasnik, Pravallika Govada, Stephen Cohen, LS Shashidhara
doi: https://doi.org/10.1101/813022
Sanket Nagarkar
1Indian Institute of Science Education and Research (IISER) Dr. Homi Bhabha Road, Pashan, Pune 411 008, INDIA
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Ruchi Wasnik
1Indian Institute of Science Education and Research (IISER) Dr. Homi Bhabha Road, Pashan, Pune 411 008, INDIA
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Pravallika Govada
1Indian Institute of Science Education and Research (IISER) Dr. Homi Bhabha Road, Pashan, Pune 411 008, INDIA
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Stephen Cohen
2Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200N Denmark
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LS Shashidhara
1Indian Institute of Science Education and Research (IISER) Dr. Homi Bhabha Road, Pashan, Pune 411 008, INDIA
3Ashoka University, Sonepat, India
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  • For correspondence: ls.shashidhara@iiserpune.ac.in
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Abstract

Promoter proximal pausing (PPP) of RNA Polymerase II has emerged as a crucial rate-limiting-step in the regulation of gene expression. Regulation of PPP is brought about by complexes 7SK snRNP, P-TEFb (Cdk9/cycT) and the Negative Elongation Factor (NELF) which are highly conserved from Drosophila to humans. Here we show that RNAi-mediated depletion of bin3 or Hexim of the 7SK snRNP complex or depletion of individual components of the NELF complex enhance Yki-driven growth leading to neoplastic transformation of Drosophila wing imaginal discs. We also show that increased CDK9 expression cooperates with Yki, in driving neoplastic growth. Interestingly, over-expression of CDK9 on its own or in the background of depletion of one of the components of 7SK snRNP or the NELF complex necessarily and specifically needed Yki over-expression to cause tumorous growth. Genome-wide gene expression analyses suggested that deregulation of protein homeostasis is associated with tumorous growth of wing imaginal discs. As both Fat/Hippo/Yki pathway and PPP are highly conserved, our observations may provide insights into mechanisms of oncogenic function of YAP, the orthologue of Yki in human.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 21, 2019.
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Promoter proximal pausing limits Yki-induced tumorous growth in Drosophila
Sanket Nagarkar, Ruchi Wasnik, Pravallika Govada, Stephen Cohen, LS Shashidhara
bioRxiv 813022; doi: https://doi.org/10.1101/813022
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Promoter proximal pausing limits Yki-induced tumorous growth in Drosophila
Sanket Nagarkar, Ruchi Wasnik, Pravallika Govada, Stephen Cohen, LS Shashidhara
bioRxiv 813022; doi: https://doi.org/10.1101/813022

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