PUBLICATION

Identification and functional evaluation of two STAT3 variants in grass carp: Implication for the existence of specific alternative splicing of STAT3 gene in teleost

Authors
Du, L., Zhou, H., Qin, L., Wei, H., Zhang, A., Yang, K., Wang, X.
ID
ZDB-PUB-170713-10
Date
2017
Source
Developmental and comparative immunology   76: 326-333 (Journal)
Registered Authors
Keywords
Functional identification, Grass carp, STAT3, Teleost-specific splicing, Variant
MeSH Terms
  • Animals
  • Lymphocytes/immunology*
  • Lipopolysaccharides/immunology
  • STAT3 Transcription Factor/genetics
  • STAT3 Transcription Factor/metabolism*
  • Carps/immunology*
  • Transcriptome
  • Signal Transduction
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism*
  • Cells, Cultured
  • Fish Proteins/genetics
  • Fish Proteins/metabolism*
  • Alternative Splicing
  • Interleukin-17/metabolism
  • Interleukin-10/metabolism
  • Immunity, Innate
  • Sequence Alignment
PubMed
28698048 Full text @ Dev. Comp. Immunol.
Abstract
A STAT family member, STAT3, becomes activated as a DNA binding protein in response to cytokines and growth factors. In teleost, STAT3 cDNA has been cloned and identified in a few species, but only a single STAT3 transcript is revealed in these studies. In the present study, two variants of STAT3 gene generated by alternative splicing were isolated from grass carp and nominated as STAT3?1 and STAT3?2 based on the homology with their mammalian orthologs. In particular, the homologs of STAT3?1/2 were also found in various fish species, including zebrafish, takifugu, tilapia, medaka and goldfish. Intriguingly, sequence alignment and genomic structure analysis revealed that fish STAT3?1/2 are generated through similar alternative splicing events, implying the potential physiological significance of generating STAT3 variants in fish. Grass carp STAT3?1/2 (gcSTAT3?1/2) were ubiquitously expressed although the transcript levels of STAT3?2 were markedly higher than STAT3?1 in all examined tissues. In vivo and in vitro studies showed that the expression patterns of these two variants were similar under the stimulation of immune stimuli. To reveal the role of gcSTAT3?1/2 in fish immunity, their phosphorylation and involvement in IL-17A/F1 mRNA expression were demonstrated in grass carp peripheral blood lymphocytes upon LPS or PHA challenge, providing evidence for the functional conservation of STAT3 signaling in fish. These findings also raise a question of whether both gcSTAT3?1/2 participate in transcriptional regulation in fish. Actually, our results showed that both of them had the ability to translocate into the nucleus upon activation, and to amplify IL-10 signaling, indicating the existence of STAT3 isoforms with functional redundancy in teleost.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping