@article{8f95e5f95a144643b8ad0318cf996048,
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′,5′-oligoadeny-late (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.",
keywords = "2-5A, Interferon, RNA decay, RNase L, Translation reprogramming",
author = "Alisha Chitrakar and Sneha Rath and Jesse Donovan and Kaitlin Demarest and Yize Li and Sridhar, {Raghavendra Rao} and Weiss, {Susan R.} and Kotenko, {Sergei V.} and Wingreen, {Ned S.} and Alexei Korennykh",
note = "Funding Information: ACKNOWLEDGMENTS. We are grateful to Bonnie Bassler (Princeton University) for help with the instrumentation for this project, Wei Wang for supervising the Icahn Genomics Institute RNA-seq facility, Gary Laevsky, director of confocal microscopy facility and Nikon center of excellence, and members of the A.K. laboratory for critically reading the manuscript, and Andrei Korostelev for important comments on the manuscript. This study was funded by Princeton University; National Institutes of Health Grants 5T32GM007388 and F99 CA212468-01 (to S.R.), 1R01 GM110161-01 (to A.K.), R01 AI104887 and NS081008 (to S.R.W.), and 1R01 AI104669 (to S.V.K.); National Science Foundation Grant PHY-1305525 (to N.S.W.); Sidney Kimmel Foundation Grant AWD1004002 (to A.K.); Burroughs Wellcome Foundation Grant 1013579 (to A.K.); and the Vallee Foundation (A.K.). Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All Rights Reserved.",
year = "2019",
month = feb,
day = "5",
doi = "10.1073/pnas.1818363116",
language = "English (US)",
volume = "116",
pages = "2103--2111",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "6",
}