Figure 7.

Impact of DENV on RBM10 and its consequences on splicing, inflammation and viral replication. Nuclear RBM10 regulates alternative splicing favoring anti-viral mRNA isoforms, among which SAT1 isoforms were investigated in this report. Upon DENV infection, NS5 intrudes into the spliceosome, as previously reported by our laboratories, and also targets RBM10 for proteasomal degradation, favoring pro-viral splicing isoforms. On the other hand, RMB10 also interacts with viral genome and RIG-I and promotes the ubiquitination of the latter, which is known to be required for its activation and the induction of the innate immune response. Overall, RBM10 is required for the induction of interferon and pro-inflammatory cytokines. Whether this is a result of RBM10 involvement in splicing regulation, or in RIG-I/DENV genome ribonucleoprotein complex, or both, remains an intriguing question. The fact is that higher protein levels of RBM10 correlate with an anti-viral, pro-inflammatory scenario while lower levels with a pro-viral, anti-inflammatory one.