E3 ligase SYVN1-Mediated Polyubiquitination of CPSF6 Promotes Alternative Polyadenylation and Antivirus Effects of Macrophages

Down-regulation of CPSF6 protein, one of 3′ end processing factors, mediates APA in macrophage with responses to virus infection and plays an important role in its anti-virus effect. However, the signal pathway and molecular mechanism underlying the downregulation of the CPSF6 protein remain elusive. Here, we found that MAVS triggers the nucleus import of E3 ligase SYVN1 mediated by NUP153 in response to vesicular stomatitis virus infection. Then, SYVN1 catalyzes K48-linked polyubiquitination of CPSF6, resulting in the degradation of CPSF6 via proteasome, and then transcriptome wide APA and anti-virus effect subsequently. Compare the changes in APA length between IVT-SAPAS groups