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dc.contributor.authorZaytseva, O
dc.contributor.authorMitchell, NC
dc.contributor.authorGuo, L
dc.contributor.authorMarshall, OJ
dc.contributor.authorParsons, LM
dc.contributor.authorHannan, RD
dc.contributor.authorLevens, DL
dc.contributor.authorQuinn, LM
dc.date.accessioned2020-11-26T23:03:36Z
dc.date.available2020-11-26T23:03:36Z
dc.date.issued2020-06-01
dc.identifierpii: 147/11/dev190231
dc.identifier.citationZaytseva, 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.
dc.identifier.issn0950-1991
dc.identifier.urihttp://hdl.handle.net/11343/252091
dc.description.abstractHere, 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.
dc.languageEnglish
dc.publisherCOMPANY BIOLOGISTS LTD
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleTranscriptional repression of Myc underlies the tumour suppressor function of AGO1 in Drosophila
dc.typeJournal Article
dc.identifier.doi10.1242/dev.190231
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.departmentAnatomy and Neuroscience
melbourne.source.titleDevelopment (Cambridge)
melbourne.source.volume147
melbourne.source.issue11
dc.rights.licenseCC BY
melbourne.elementsid1453665
melbourne.contributor.authorQuinn, Leonie
melbourne.contributor.authorHannan, Ross
dc.identifier.eissn1477-9129
melbourne.accessrightsOpen Access


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