Concerted 2-5A-Mediated mRNA Decay and Transcription Reprogram Protein Synthesis in dsRNA Response

Sneha Rath; Eliza Prangley; Jesse Donovan; Kaitlin Demarest; Yigal Meir; Ned Wingreen; Alexei Korennykh

As basal mRNAs decay, defense mRNAs encoding IFNs and ISGs are upregulated (Fig. 6A ). The mRNAs are initially absent, but by four hours IFN/ISG mRNAs account for 25% of the poly-A + pool. In log-linear coordinates, the loss of basal mRNAs and the increase in innate immune transcripts obeys a linear law (Fig. 6C, S7A ). The induction of defense transcripts bypasses RNase L ( Fig. 6D ; S6A; S7A), as previously reported (Alisha Chitrakar et al., 2018) . To test whether defense mRNAs . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/484675 doi: bioRxiv preprint could survive in the presence of RNase L, we measured their decay kinetics during 2-5AMD in the presence of actinomycin D treatment, which was used to stop new transcription (Fig. 6E ). RNase L-dependent decay of the innate immune mRNAs was readily detected ( Fig. 6F ; S6B), indicating that defense mRNAs can be cleaved by RNase L. However, the decay half-lives (T 1/2 ) for defense mRNAs were ~2-3-fold longer compared to those of basal mRNAs (Fig. 6F ).