The atypical kinase riok3 limits rvfv propagation and is regulated by alternative splicing

Katherine E. Havranek, Luke Adam White, Thomas C. Bisom, Jean Marc Lanchy, J. Stephen Lodmell

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

In recent years, transcriptome profiling studies have identified changes in host splicing patterns caused by viral invasion, yet the functional consequences of the vast majority of these splicing events remain uncharacterized. We recently showed that the host splicing landscape changes during Rift Valley fever virus MP-12 strain (RVFV MP-12) infection of mammalian cells. Of particular interest, we observed that the host mRNA for Rio Kinase 3 (RIOK3) was alternatively spliced during infection. This kinase has been shown to be involved in pattern recognition receptor (PRR) signaling mediated by RIG-I like receptors to produce type-I interferon. Here, we characterize RIOK3 as an important component of the interferon signaling pathway during RVFV infection and demonstrate that RIOK3 mRNA expression is skewed shortly after infection to produce alternatively spliced variants that encode premature termination codons. This splicing event plays a critical role in regulation of the antiviral response. Interestingly, infection with other RNA viruses and transfection with nucleic acid-based RIG-I agonists also stimulated RIOK3 alternative splicing. Finally, we show that specifically stimulating alternative splicing of the RIOK3 transcript using a morpholino oligonucleotide reduced interferon expression. Collectively, these results indicate that RIOK3 is an important component of the mammalian interferon signaling cascade and its splicing is a potent regulatory mechanism capable of fine-tuning the host interferon response.

Original languageEnglish
Article number367
JournalViruses
Volume13
Issue number3
DOIs
StatePublished - Mar 2021

Keywords

  • Alternative splicing
  • Innate immune response
  • MP-12
  • Morpholino oligonucleotide
  • RIOK3
  • Rift Valley fever virus

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