@article{3543,
  keywords = {Protein Biosynthesis, Structure-Activity Relationship, Humans, Cell Line, Protein Binding, Models, Molecular, Protein Conformation, Biosensing Techniques, Protein Interaction Domains and Motifs, Endoribonucleases, Interferons, Interferon-beta},
  author = {Alisha Chitrakar and Sneha Rath and Jesse Donovan and Kaitlin Demarest and Yize Li and Raghavendra Sridhar and Susan Weiss and Sergei Kotenko and Ned Wingreen and Alexei Korennykh},
  title = {Real-time 2-5A kinetics suggest that interferons β and λ evade global arrest of translation by RNase L.},
  abstract = { <p>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.</p> },
  year = {2019},
  journal = {Proc Natl Acad Sci U S A},
  volume = {116},
  pages = {2103-2111},
  month = {2019 Feb 05},
  issn = {1091-6490},
  doi = {10.1073/pnas.1818363116},
  language = {eng},
}