@article{200756,
  keywords = {Humans, Immunity, Innate, A549 Cells, Endoribonucleases/genetics/*metabolism, *Protein Biosynthesis, *RNA Stability, RNA, Double-Stranded/genetics/*metabolism, RNA, Messenger/genetics/*metabolism, *Transcription, Genetic, *RNase L, *dsRNA, *innate immunity, *interferon, *mRNA decay, *reprogramming, *translation},
  author = {S. Rath and E. Prangley and J. Donovan and K. Demarest and N. S. Wingreen and Y. Meir and A. Korennykh},
  title = {Concerted 2-5A-Mediated mRNA Decay and Transcription Reprogram Protein Synthesis in the dsRNA Response},
  abstract = { Viral and endogenous double-stranded RNA (dsRNA) is a potent trigger for programmed RNA degradation by the 2-5A/RNase L complex in cells of all mammals. This 2-5A-mediated decay (2-5AMD) is a conserved stress response switching global protein synthesis from homeostasis to production of interferons (IFNs). To understand this mechanism, we examined 2-5AMD in human cells and found that it triggers polysome collapse characteristic of inhibited translation initiation. We determined that translation initiation complexes and ribosomes purified from translation-arrested cells remain functional. However, spike-in RNA sequencing (RNA-seq) revealed cell-wide decay of basal mRNAs accompanied by rapid accumulation of mRNAs encoding innate immune proteins. Our data attribute this 2-5AMD evasion to better stability of defense mRNAs and positive feedback in the IFN response amplified by RNase L-resistant molecules. We conclude that 2-5AMD and transcription act in concert to refill mammalian cells with defense mRNAs, thereby "prioritizing" the synthesis of innate immune proteins. },
  year = {2019},
  journal = {Mol Cell},
  volume = {75},
  edition = {20190904},
  number = {6},
  pages = {1218-1228.e6},
  month = {09/2019},
  isbn = {1097-2765 (Print)1097-2765},
  language = {eng},
}