TY  - JOUR
AU  - Kang, J
AU  - Kusnadi, EP
AU  - Ogden, AJ
AU  - Hicks, RJ
AU  - Bammert, L
AU  - Kutay, U
AU  - Hung, S
AU  - Sanij, E
AU  - Hannan, RD
AU  - Hannan, KM
AU  - Pearson, RB
Y2  - 2021/02/05
Y1  - 2016/08/02
SN  - 1949-2553
UR  - http://hdl.handle.net/11343/259980
AB  - 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 factor-dependent 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.
LA  - English
PB  - IMPACT JOURNALS LLC
T1  - Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription
DO  - 10.18632/oncotarget.10346
IS  - Oncotarget
VL  - 7
IS  - 31
SP  - 48887-48904
OP  - 509087
OP  - 566876
OP  - 1053792
OP  - 566771
OP  - 1003270
OP  - 1038852
L1  - /bitstream/handle/11343/259980/PMC5226478.pdf?sequence=1&isAllowed=y
ER  -