RT Journal Article SR Electronic T1 Glutamine deficiency in solid tumors confers resistance to ribosomal RNA synthesis inhibitors JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.12.03.471189 DO 10.1101/2021.12.03.471189 A1 Melvin Pan A1 Christiane Zorbas A1 Maki Sugaya A1 Kensuke Ishiguro A1 Miki Kato A1 Miyuki Nishida A1 Hai-Feng Zhang A1 Marco M Candeias A1 Akimitsu Okamoto A1 Takamasa Ishikawa A1 Tomoyoshi Soga A1 Hiroyuki Aburatani A1 Juro Sakai A1 Yoshihiro Matsumura A1 Tsutomu Suzuki A1 Christopher G. Proud A1 Denis L. J. Lafontaine A1 Tsuyoshi Osawa YR 2021 UL http://biorxiv.org/content/early/2021/12/04/2021.12.03.471189.abstract AB Ribosome biogenesis involves the processing of precursor ribosomal RNAs (pre-rRNAs) and sequential assembly with ribosomal proteins. Here we report that nutrient deprivation severely impairs pre-rRNA processing and leads to the accumulation of unprocessed rRNAs. Upon nutrient restoration, the accumulated pre-rRNAs are processed into mature rRNAs that are utilized for ribosome biogenesis. Failure to accumulate pre-rRNAs under nutrient deprivation leads to perturbed ribosome assembly during nutrient restoration and subsequent apoptosis via uL5/uL18-mediated activation of p53. Restoration of glutamine alone activates p53 by triggering uL5/uL18 translation. Induction of uL5/uL18 protein synthesis by glutamine was dependent on the translation factor eukaryotic elongation factor 2 (eEF2), which was in turn dependent on Raf/MEK/ERK signalling. Depriving cells of glutamine prevents the activation of p53 by rRNA synthesis inhibitors. Our data reveals a mechanism that cancer cells can exploit to suppress p53-mediated apoptosis during fluctuations in environmental nutrient availability.Competing Interest StatementThe authors have declared no competing interest.