PT  - JOURNAL ARTICLE
AU  - Sanket Nagarkar
AU  - Ruchi Wasnik
AU  - Pravallika Govada
AU  - Stephen Cohen
AU  - LS Shashidhara
TI  - Promoter proximal pausing limits Yki-induced tumorous growth in <em>Drosophila</em>
AID  - 10.1101/813022
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 813022
4099  - http://biorxiv.org/content/early/2019/10/21/813022.short
4100  - http://biorxiv.org/content/early/2019/10/21/813022.full
AB  - 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.