RT Journal Article
SR Electronic
T1 Adaptive translational pausing is a hallmark of the cellular response to severe environmental stress
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.10.334375
DO 10.1101/2020.10.10.334375
A1 Raul Jobava
A1 Yuanhui Mao
A1 Bo-Jhih Guan
A1 Dawid Krokowski
A1 Erica Shu
A1 Di Hu
A1 Evelyn Chukwurah
A1 Jing Wu
A1 Zhaofeng Gao
A1 Leah L. Zagore
A1 William C. Merrick
A1 Youwei Zhang
A1 Xin Qi
A1 Eckhard Jankowsky
A1 Ivan Topisirovic
A1 Donny D. Licatalosi
A1 Shu-Bing Qian
A1 Maria Hatzoglou
YR 2020
UL http://biorxiv.org/content/early/2020/10/10/2020.10.10.334375.abstract
AB Mammalian cells have to adapt to environmental challenges that range from mild to severe stress. While the cellular response to mild stress has been widely studied, how cells respond to severe stress remains unclear. We show here that under severe stress conditions, cells induce a transient hibernation-like mechanism that anticipates recovery. We demonstrate that this Adaptive Pausing Response (APR) is a coordinated cellular response that limits ATP supply and consumption though mitochondrial fragmentation and widespread pausing of mRNA translation. This pausing is accomplished by ribosome stalling at translation initiation codons, which keeps mRNAs poised to resume translation upon recovery from severe stress. We further show that recovery from severe stress involves adaptive ISR (Integrated Stress Response) signaling that in turn permits cell cycle progression, resumption of growth, and reversal of mitochondria fragmentation. Our findings indicate that cells can respond to severe stress through the APR, a mechanism that preserves vital elements of cellular function under harsh environmental conditions.Competing Interest StatementThe authors have declared no competing interest.