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Published online December 17, 2007
doi:10.1083/jcb.200709044
The Journal of Cell Biology, Vol. 179, No. 6, 1105-1113
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Grewal et al.
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Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway

Savraj S. Grewal, Justin R. Evans, and Bruce A. Edgar

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109

Correspondence to Savraj S. Grewal: grewalss{at}ucalgary.ca; or Bruce A. Edgar: bedgar{at}fhcrc.org

Synthesis of ribosomal RNA (rRNA) is a key step in ribosome biogenesis and is essential for cell growth. Few studies, however, have investigated rRNA synthesis regulation in vivo in multicellular organisms. Here, we present a genetic analysis of transcription initiation factor IA (TIF-IA), a conserved RNA polymerase I transcription factor. Drosophila melanogaster Tif-IA–/– mutants have reduced levels of rRNA synthesis and sustain a developmental arrest caused by a block in cellular growth. We find that the target of rapamycin (TOR) pathway regulates TIF-IA recruitment to rDNA. Furthermore, we show that the TOR pathway regulates rRNA synthesis in vivo and that TIF-IA overexpression can maintain rRNA transcription when TOR activity is reduced in developing larvae. We propose that TIF-IA acts in vivo as a downstream growth–regulatory target of the TOR pathway. Overexpression of TIF-IA also elevates levels of both 5S RNA and messenger RNAs encoding ribosomal proteins. Stimulation of rRNA synthesis by TIF-IA may therefore provide a feed-forward mechanism to coregulate the levels of other ribosome components.

S.S. Grewal's present address is Dept. of Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary Health Research Innovation Center, Calgary, Canada T2N 4N1.

Abbreviations used in this paper: eIF4E, eukaryotic translation initiation factor 4E; ETS, external transcribed spacer; GPDH, glycerol 3–phosphate dehydrogenase; RP, ribosomal protein; rRNA, ribosomal RNA; S6K, S6 kinase; TIF-IA, transcription initiation factor IA; TOR, target of rapamycin; UAS, upstream activator sequence; UBF, upstream binding factor.


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