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bioRxiv · 10.1101/813022

Promoter proximal pausing limits Yki-induced tumorous growth in Drosophila

Nagarkar, S.·Wasnik, R.·Govada, P.·Cohen, S. M.·SHASHIDHARA, L. S.
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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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Nagarkar, S., Wasnik, R., Govada, P., Cohen, S. M., SHASHIDHARA, L. S.. 2019-10-21. Promoter proximal pausing limits Yki-induced tumorous growth in Drosophila. https://doi.org/10.1101/813022

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