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|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'-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.|
|Citation:||Chitrakar, Alisha, Rath, Sneha, Donovan, Jesse, Demarest, Kaitlin, Li, Yize, Sridhar, Raghavendra Rao, Weiss, Susan R, Kotenko, Sergei V, Wingreen, Ned S, Korennykh, Alexei. (2019). Real-time 2-5A kinetics suggest that interferons β and λ evade global arrest of translation by RNase L.. Proceedings of the National Academy of Sciences of the United States of America, 116 (6), 2103 - 2111. doi:10.1073/pnas.1818363116|
|Pages:||1 - 37|
|Type of Material:||Journal Article|
|Journal/Proceeding Title:||Proceedings of the National Academy of Sciences of the United States of America|
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