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

Initial studies of 2-5AMD in rabbit reticulocyte lysate (RRL) reported polysome disaggregation and degradation of mRNAs (Clemens and Williams, 1978) . RRL does not have transcription, which limits biologic interpretations of these results: in the cellfree system, the loss of mRNAs and polysomes due to a non-specific RNase is inevitable. In live cells, 2-5AMD has sufficient potency to cause degradation of 18S and 28S rRNAs. The characteristic rRNA cleavage pattern provides a reliable readout of RNase L activation Malathi et al., 2007) . Furthermore, 2-5AMD causes degradation of tRNA-His and tRNA-Pro, as well as multiple mRNAs in live cells (Al-Ahmadi et al., 2009; Le Roy et al., 2007; Rath et al., 2015) .