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

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    Author
    Zaytseva, O; Mitchell, NC; Guo, L; Marshall, OJ; Parsons, LM; Hannan, RD; Levens, DL; Quinn, LM
    Date
    2020-06-01
    Source Title
    Development (Cambridge)
    Publisher
    COMPANY BIOLOGISTS LTD
    University of Melbourne Author/s
    Quinn, Leonie; Hannan, Ross
    Affiliation
    Sir Peter MacCallum Department of Oncology
    Anatomy and Neuroscience
    Metadata
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    Document Type
    Journal Article
    Citations
    Zaytseva, O., Mitchell, N. C., Guo, L., Marshall, O. J., Parsons, L. M., Hannan, R. D., Levens, D. L. & Quinn, L. M. (2020). Transcriptional repression of Myc underlies the tumour suppressor function of AGO1 in Drosophila. DEVELOPMENT, 147 (11), https://doi.org/10.1242/dev.190231.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/252091
    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 Myc abundance. 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.

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