title: Regulation of rDNA transcription in response to growth factors, nutrients and energy.
abstract: Exquisite control of ribosome biogenesis is fundamental for the maintenance of cellular growth and proliferation. Importantly, synthesis of ribosomal RNA by RNA polymerase I is a key regulatory step in ribosome biogenesis and a major biosynthetic and energy consuming process. Consequently, ribosomal RNA gene transcription is tightly coupled to the availability of growth factors, nutrients and energy. Thus cells have developed an intricate sensing network to monitor the cellular environment and modulate ribosomal DNA transcription accordingly. Critical controllers in these sensing networks, which mediate growth factor activation of ribosomal DNA transcription, include the PI3K/AKT/mTORC1, RAS/RAF/ERK pathways and MYC transcription factor. mTORC1 also responds to amino acids and energy status, making it a key hub linking all three stimuli to the regulation of ribosomal DNA transcription, although this is achieved via overlapping and distinct mechanisms. This review outlines the current knowledge of how cells respond to environmental cues to control ribosomal RNA synthesis. We also highlight the critical points within this network that are providing new therapeutic opportunities for treating cancers through modulation of RNA polymerase I activity and potential novel imaging strategies.
authors.affiliation: Division of Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Kusnadi
authors.affiliation: Division of Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Hannan
authors.affiliation: Division of Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.affiliation: Division of Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168, Australia; School of Biomedical Sciences, University of Queensland, Queensland 4072, Australia. Electronic address: ross.hannan@petermac.org.
authors.forename: Ross D
authors.initials: RD
authors.lastname: Hannan
authors.affiliation: Division of Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia; Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168, Australia. Electronic address: rick.pearson@petermac.org.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pearson
authors.affiliation: Division of Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004275:DNA, Ribosomal / Q000235:genetics*; D004734:Energy Metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D012318:RNA Polymerase I / Q000378:metabolism; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D012270:Ribosomes / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000596:Amino Acids; D004275:DNA, Ribosomal; D036341:Intercellular Signaling Peptides and Proteins; D012335:RNA, Ribosomal; D000255:Adenosine Triphosphate; D012318:RNA Polymerase I
keywords: Amino acids; Energy; Growth factors; Nutrients; mTORC1; rDNA transcription