@article{200766,
  keywords = {Models, Molecular, Protein Conformation, Humans, Structure-Activity Relationship, Cell Line, Protein Binding, Protein Interaction Domains and Motifs, *Protein Biosynthesis, *RNase L, *interferon, *Biosensing Techniques, Endoribonucleases/*chemistry/metabolism, Interferon-beta/*chemistry/metabolism, Interferons/*chemistry/metabolism, *2-5a, *RNA decay, *translation reprogramming},
  author = {A. Chitrakar and S. Rath and J. Donovan and K. Demarest and Y. Li and R. R. Sridhar and S. R. Weiss and S. V. Kotenko and N. S. Wingreen and A. Korennykh},
  title = {Real-time 2-5A kinetics suggest that interferons β and λ evade global arrest of translation by RNase L},
  abstract = { Cells of all mammals recognize double-stranded RNA (dsRNA) as a foreign material. In response, they release interferons (IFNs) and activate a ubiquitously expressed pseudokinase/endoribonuclease RNase L. RNase L executes regulated RNA decay and halts global translation. Here, we developed a biosensor for 2{\textquoteright},5{\textquoteright}-oligoadenylate (2-5A), the natural activator of RNase L. Using this biosensor, we found that 2-5A was acutely synthesized by cells in response to dsRNA sensing, which immediately triggered cellular RNA cleavage by RNase L and arrested host protein synthesis. However, translation-arrested cells still transcribed IFN-stimulated genes and secreted IFNs of types I and III (IFN-β and IFN-λ). Our data suggest that IFNs escape from the action of RNase L on translation. We propose that the 2-5A/RNase L pathway serves to rapidly and accurately suppress basal protein synthesis, preserving privileged production of defense proteins of the innate immune system. },
  year = {2019},
  journal = {Proc Natl Acad Sci U S A},
  volume = {116},
  edition = {20190117},
  number = {6},
  pages = {2103-2111},
  month = {02/2019},
  isbn = {0027-8424 (Print)0027-8424},
  language = {eng},
}