title: Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway.
abstract: 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.
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. grewalss@ucalgary.ca
authors: Savraj S
authors: SS
authors: Grewal
authors: Justin R
authors: JR
authors: Evans
authors: Bruce A
authors: BA
authors: Edgar
mesh_terms: D000818:Animals; D049108:Cell Enlargement; D004275:DNA, Ribosomal / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D007814:Larva / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011494:Protein Kinases; D012322:RNA Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012335:RNA, Ribosomal / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D004275:DNA, Ribosomal; D029721:Drosophila Proteins; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D012322:RNA Precursors; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; C526066:Tif-IA protein, Drosophila; C416303:target of rapamycin protein, Drosophila