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Transcriptional repression of Myc underlies the tumour suppressor function of AGO1 in Drosophila

Citation

Zaytseva, O and Mitchell, NC and Guo, L and Marshall, OJ and Parsons, LM and Hannan, RD and Levens, DL and Quinn, LM, Transcriptional repression of Myc underlies the tumour suppressor function of AGO1 in Drosophila, Development (Cambridge, England), 147, (11) pp. 1-11. ISSN 0950-1991 (2020) [Refereed Article]


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This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

DOI: doi:10.1242/dev.190231

Abstract

Here, we report novel tumour suppressor activity for the Drosophila Argonaute family RNA-binding protein AGO1, a component of the miRNA-dependent RNA-induced silencing complex (RISC). The mechanism for growth inhibition does not, however, involve canonical roles as part of the RISC; rather, AGO1 controls cell and tissue growth by functioning as a direct transcriptional repressor of the master regulator of growth, Myc. AGO1 depletion in wing imaginal discs drives a significant increase in ribosome biogenesis, nucleolar expansion and cell growth in a manner dependent on Mycabundance. Moreover, increased Myc promoter activity and elevated Myc mRNA in AGO1-depleted animals requires RNA polymerase II transcription. Further support for transcriptional AGO1 functions is provided by physical interaction with the RNA polymerase II transcriptional machinery (chromatin remodelling factors and Mediator Complex), punctate nuclear localisation in euchromatic regions and overlap with Polycomb Group transcriptional silencing loci. Moreover, significant AGO1 enrichment is observed on the Myc promoter and AGO1 interacts with the Myc transcriptional activator Psi. Together, our data show that Drosophila AGO1 functions outside of the RISC to repress Myc transcription and inhibit developmental cell and tissue growth. This article has an associated 'The people behind the papers' interview.

Item Details

Item Type:Refereed Article
Keywords:Argonaute, Drosophila, Myc, proliferation, Psi, transcription
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell development, proliferation and death
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Marshall, OJ (Dr Owen Marshall)
UTAS Author:Parsons, LM (Dr Linda Parsons)
ID Code:152315
Year Published:2020
Web of Science® Times Cited:3
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-08-17
Last Modified:2022-09-08
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