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Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development


Regulating ribosome number is thought to control cellular growth1. Synthesis of ribosomal RNA (rRNA) is a limiting step in ribosome biogenesis and rates of rRNA synthesis are generally altered depending on the growth status of a cell2,3. Although studies in unicellular systems have addressed the mechanisms by which this occurs4,5, few studies have applied a genetic approach to examine growth-dependent control of rRNA synthesis in metazoans. Here, we show that in Drosophila melanogaster Myc (dMyc) is a regulator of rRNA synthesis. Expression of dMyc is both necessary and sufficient to control rRNA synthesis and ribosome biogenesis during larval development. Stimulation of rRNA synthesis by dMyc is mediated through a rapid, coordinated increase in the levels of the Pol I transcriptional machinery. In addition, the growth effects of dMyc in larval wing imaginal discs require de novo rRNA synthesis. We suggest that during animal development, the control of rRNA synthesis and ribosome biogenesis is an essential Myc function.

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The authors would like to thank L. Saucedo, C. Grandori and R. White for helpful advice and comments on the manuscript and C. Grandori and R. White for sharing unpublished data. S.S.G. is supported by a research fellowship from the SASS Foundation for Medical Research. A.O. is a Leukemia & Lymphoma Society Special Fellow. R.N.E is an American Cancer Society Research Professor. This work was supported by a National Institutes of Health (NIH)/National Cancer Institute grant R01CA57138 (to R.N.E.) and an NIH grant GM51186 (to B.A.E).

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The authors declare no competing financial interests.

Correspondence to Bruce A. Edgar.

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Figure 1: Pol I activity is required for normal development and growth.
Figure 2: dMyc regulates rRNA synthesis during D. melanogaster development.
Figure 3: Overexpression of dMyc increases nucleolar size and cellular ribosome content in salivary-gland cells.
Figure 4: dMyc overexpression increases levels of the rRNA transcriptional machinery.
Figure 5: dMyc requires increased rRNA synthesis for growth.