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Promoter Proximal Pausing Limits Tumorous Growth Induced by the Yki Transcription Factor in Drosophila
- Source :
- Genetics, Nagarkar, S, Wasnik, R, Govada, P, Cohen, S & Shashidhara, L S 2020, ' Promoter proximal pausing limits tumorous growth induced by the yki transcription factor in drosophila ', Genetics, vol. 216, no. 1, pp. 67-77 . https://doi.org/10.1534/genetics.120.303419
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
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 enhances 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, overexpression 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 overexpression 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 ortholog of Yki in humans.
- Subjects :
- Carcinogenesis
Hippo pathway
Gene Expression
RNA polymerase II
Investigations
Biology
transcription regulation in growth and cancer
NELF complex
03 medical and health sciences
0302 clinical medicine
Transcription regulation in growth
Genetics
Animals
Drosophila Proteins
Wings, Animal
Neoplastic transformation
Promoter proximal pausing
Negative elongation factor
Promoter Regions, Genetic
Transcription factor
Cancer
030304 developmental biology
Regulation of gene expression
0303 health sciences
Hippo signaling pathway
promoter proximal pausing
fungi
Nuclear Proteins
RNA-Binding Proteins
YAP-Signaling Proteins
Methyltransferases
Cyclin-Dependent Kinase 9
Cell biology
body regions
Gene Expression Regulation, Neoplastic
tumorigenesis
Imaginal disc
Drosophila melanogaster
Imaginal Discs
Tumorigenesis
Trans-Activators
biology.protein
Drosophila
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 19432631
- Volume :
- 216
- Database :
- OpenAIRE
- Journal :
- Genetics
- Accession number :
- edsair.doi.dedup.....ebec06a08e7a0385055252d81274018d