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

Gene. 2015 Feb 1;556(1):27-34. doi: 10.1016/j.gene.2014.11.010. Epub 2014 Nov 8.


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.

Keywords: Amino acids; Energy; Growth factors; Nutrients; mTORC1; rDNA transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acids / metabolism
  • Animals
  • DNA, Ribosomal / genetics*
  • Energy Metabolism / physiology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Neoplasms / drug therapy
  • Neoplasms / enzymology
  • RNA Polymerase I / metabolism
  • RNA, Ribosomal / biosynthesis*
  • Ribosomes / metabolism
  • Transcription, Genetic / drug effects*


  • Amino Acids
  • DNA, Ribosomal
  • Intercellular Signaling Peptides and Proteins
  • RNA, Ribosomal
  • Adenosine Triphosphate
  • RNA Polymerase I