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. and Pearson, Richard B. (2016) Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription. Oncotarget, 7 31: 48887-48904. doi:10.18632/oncotarget.10346


Author 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.
Title Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription
Journal name Oncotarget   Check publisher's open access policy
ISSN 1949-2553
Publication date 2016-06-30
Sub-type Article (original research)
DOI 10.18632/oncotarget.10346
Open Access Status DOI
Volume 7
Issue 31
Start page 48887
End page 48904
Total pages 18
Place of publication Albany, NY, United States
Publisher Impact Journals LLC
Language eng
Subject 2730 Oncology
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.
Keyword Amino acids
Gerotarget
MYC
RDNA transcription
S6K1
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
 
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