Arenaviridae exoribonuclease presents genomic RNA edition capacity

Elsie Yekwa; Chutima Aphibanthammakit; Xavier Carnec; Bruno Coutard; Caroline Picard; Bruno Canard; Sylvain Baize; François Ferron

We measured NP-exo MOPV and NP-exo LCMV's ability to cleave different ds RNA substrates. Because the key enzyme in the innate immune response; the protein kinase RNAactivated (PKR); is induced by the presence of ds RNA, we made use of a perfectly annealed ds RNA, as well as several potential RNA substrates such as those mimicking an erroneous replication product with one, two or three mismatched nucleotides at the 3'-end. To that end, a 40-mer RNA The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/541698 doi: bioRxiv preprint template (RT1) blocked in 3'-end with a phosphate group was annealed to a radiolabeled RNA carrying zero (RL2*) or one (RL3*), two (RL4*) or three (RL5*) non-complementary nucleotides at its 3'-end as shown in Fig 4A. Fig 4B shows that both enzymes are strict ds RNA ExoNs, with the interesting specific ability to digest substrates carrying a single 3'-terminal mismatch (RL3*/RT1).