Realtime 2-5A kinetics suggests interferons ß and ? evade global arrest of translation by RNase L

Alisha Chitrakar; Sneha Rath; Jesse Donovan; Kaitlin Demarest; Yize Li; Raghavendra Rao Sridhar; Susan R. Weiss; Sergei V. Kotenko; Ned S. Wingreen; Alexei Korennykh

The pathways of 2-5A and IFNs are closely interconnected. IFNs stimulate 2-5A production by transcriptionally inducing the OASs 3,34,35 . Conversely, 2-5A can amplify 36 and suppress 37 IFN-β protein production. Considering that RNase L stops translation and ultimately causes apoptosis 38 The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/476341 doi: bioRxiv preprint contrast, transcription of IFN stimulated genes (ISGs) measured by qPCR of OAS1/2/3/L and the helicases RIG-I and MDA5, developed with a lag of 2-4 hours and became strong after maximal 2-5A production (Fig. 4, A and B) . Rapid 2-5A synthesis before the IFN response was confirmed by cleavage of 28S rRNA in A549 cells (Fig. 4C ), and in HeLa cells using a combination of biosensor and qPCR readouts ( fig. S4 ).