Journal article

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

Olga Zaytseva, Naomi C Mitchell, Linna Guo, Owen J Marshall, Linda M Parsons, Ross D Hannan, David L Levens, Leonie M Quinn

DEVELOPMENT | COMPANY BIOLOGISTS LTD | Published : 2020

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 polymera..

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