Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription

Jian Kang, Eric P Kusnadi, Allison J. Ogden, Rodney J. Hicks, Lukas Bammert, Ulrike Kutay, Sandy Hung, Elaine Sanij, Ross D. Hannan, Katherine M Hannan, Richard B. Pearson

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

Abstract

Dysregulation of RNA polymerase I (Pol I)-dependent ribosomal DNA (rDNA) transcription is a consistent feature of malignant transformation that can be targeted to treat cancer. Understanding how rDNA transcription is coupled to the availability of growth factors and nutrients will provide insight into how ribosome biogenesis is maintained in a tumour environment characterised by limiting nutrients. We demonstrate that modulation of rDNA transcription initiation, elongation and rRNA processing is an immediate, co-regulated response to altered amino acid abundance, dependent on both mTORC1 activation of S6K1 and MYC activity. Growth factors regulate rDNA transcription initiation while amino acids modulate growth factordependent rDNA transcription by primarily regulating S6K1-dependent rDNA transcription elongation and processing. Thus, we show for the first time amino acids regulate rRNA synthesis by a distinct, post-initiation mechanism, providing a novel model for integrated control of ribosome biogenesis that has implications for understanding how this process is dysregulated in cancer.

Original languageEnglish
Pages (from-to)48887-48904
Number of pages18
JournalOncotarget
Volume7
Issue number31
DOIs
Publication statusPublished - 2016

Keywords

  • Amino acids
  • Gerotarget
  • MYC
  • rDNA transcription
  • S6K1

Cite this

Kang, Jian ; Kusnadi, Eric P ; Ogden, Allison J. ; Hicks, Rodney J. ; Bammert, Lukas ; Kutay, Ulrike ; Hung, Sandy ; Sanij, Elaine ; Hannan, Ross D. ; Hannan, Katherine M ; Pearson, Richard B. / Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription. In: Oncotarget. 2016 ; Vol. 7, No. 31. pp. 48887-48904.
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abstract = "Dysregulation of RNA polymerase I (Pol I)-dependent ribosomal DNA (rDNA) transcription is a consistent feature of malignant transformation that can be targeted to treat cancer. Understanding how rDNA transcription is coupled to the availability of growth factors and nutrients will provide insight into how ribosome biogenesis is maintained in a tumour environment characterised by limiting nutrients. We demonstrate that modulation of rDNA transcription initiation, elongation and rRNA processing is an immediate, co-regulated response to altered amino acid abundance, dependent on both mTORC1 activation of S6K1 and MYC activity. Growth factors regulate rDNA transcription initiation while amino acids modulate growth factordependent rDNA transcription by primarily regulating S6K1-dependent rDNA transcription elongation and processing. Thus, we show for the first time amino acids regulate rRNA synthesis by a distinct, post-initiation mechanism, providing a novel model for integrated control of ribosome biogenesis that has implications for understanding how this process is dysregulated in cancer.",
keywords = "Amino acids, Gerotarget, MYC, rDNA transcription, S6K1",
author = "Jian Kang and Kusnadi, {Eric P} and Ogden, {Allison J.} and Hicks, {Rodney J.} and Lukas Bammert and Ulrike Kutay and Sandy Hung and Elaine Sanij and Hannan, {Ross D.} and Hannan, {Katherine M} and Pearson, {Richard B.}",
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Kang, J, Kusnadi, EP, Ogden, AJ, Hicks, RJ, Bammert, L, Kutay, U, Hung, S, Sanij, E, Hannan, RD, Hannan, KM & Pearson, RB 2016, 'Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription', Oncotarget, vol. 7, no. 31, pp. 48887-48904. https://doi.org/10.18632/oncotarget.10346

Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription. / Kang, Jian; Kusnadi, Eric P; Ogden, Allison J.; Hicks, Rodney J.; Bammert, Lukas; Kutay, Ulrike; Hung, Sandy; Sanij, Elaine; Hannan, Ross D.; Hannan, Katherine M; Pearson, Richard B.

In: Oncotarget, Vol. 7, No. 31, 2016, p. 48887-48904.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Hicks, Rodney J.

AU - Bammert, Lukas

AU - Kutay, Ulrike

AU - Hung, Sandy

AU - Sanij, Elaine

AU - Hannan, Ross D.

AU - Hannan, Katherine M

AU - Pearson, Richard B.

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