Regulation of rDNA transcription in response to growth factors, nutrients and energy.

Exquisite control of ribosome biogenesisis fundamental for the maintenance of cellular growth and proliferation. Importantly, synthesis of ribosomal RNAby RNA polymerase Iis a key regulatory step in ribosome biogenesisand a major biosynthetic and energy consuming process. Consequently, ribosomal RNAgene 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 DNAtranscription accordingly. Critical controllers in these sensing networks, which mediate growth factor activation of ribosomal DNAtranscription, include the PI3K/AKT/ mTORC1, RAS/RAF/ERK pathways and MYC transcription factor. mTORC1also responds to amino acids and energy status, making it a key hub linking all three stimuli to the regulation of ribosomal DNAtranscription, 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 RNAsynthesis. We also highlight the critical points within this network that are providing new therapeutic opportunities for treating cancers through modulation of RNA polymerase Iactivity and potential novel imaging strategies.