MAVS splicing variants associated with TRAF3 and TRAF6 in NF-κB and IRF3 signaling pathway in large yellow croaker Larimichthys crocea

Dev Comp Immunol. 2021 Aug:121:104076. doi: 10.1016/j.dci.2021.104076. Epub 2021 Mar 23.

Abstract

Mitochondrial antiviral signaling protein (MAVS) acts as an essential adaptor in host RIG-I-like receptors (RLRs) mediated antiviral signaling pathway. In the present study, two MAVS transcript variants, the typical form and a splicing variant, namely Lc-MAVS_tv1 and Lc-MAVS_tv2 were characterized in large yellow croaker (Larimichthys crocea). The putative Lc-MAVS_tv1 protein contains 512 aa, with an N-terminal CARD domain, a central proline-rich region, and a C-terminal transmembrane (TM) domain, whereas Lc-MAVS_tv2 contains 302 aa and lacks the C-terminal TM domain due to a premature stop in the 102 bp intron fragment insertion. Lc-MAVS_tv1 was identified as a mitochondrion localized protein whereas Lc-MAVS_tv2 exhibited an entire cytosolic distribution. Quantitative real-time PCR revealed that Lc-MAVS_tv1 mRNA was broadly expressed in examined organs/tissues and showed extremely higher level than that of Lc-MAVS_tv2, and both of them could be up-regulated under poly I:C, LPS, PGN, and Pseudomonas plecoglossicida stimulation in vivo. Interestingly, overexpression of Lc-MAVS_tv2 could induce the activation of NF-κB but not IRF3, and Lc-MAVS_tv2 co-transfected with Lc-MAVS_tv1 induced a significantly higher level of NF-κB and IRF3 promoter activity. In addition, Lc-MAVS_tv2 overexpression could enhance TRAF3 and TRAF6 mediated NF-κB activation, but suppress TRAF3 and TRAF6 mediated IRF3 activation, implying that the splicing variant Lc-MAVS_tv2 may function as an important regulator in MAVS mediated signaling pathway.

Keywords: IRF3; Large yellow croaker; MAVS; NF-κB; Splicing variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence / genetics
  • Animals
  • Fish Proteins / genetics
  • Fish Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Immunity, Innate*
  • Interferon Regulatory Factor-3 / metabolism
  • Lipopolysaccharides / immunology
  • NF-kappa B / metabolism
  • Perciformes / genetics
  • Perciformes / immunology*
  • Perciformes / microbiology
  • Poly I-C / immunology
  • Pseudomonas / immunology
  • RNA Splicing / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • TNF Receptor-Associated Factor 3 / metabolism
  • TNF Receptor-Associated Factor 6 / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Fish Proteins
  • Interferon Regulatory Factor-3
  • Lipopolysaccharides
  • NF-kappa B
  • TNF Receptor-Associated Factor 3
  • TNF Receptor-Associated Factor 6
  • Poly I-C

Supplementary concepts

  • Pseudomonas plecoglossicida