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Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway
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.
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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