Identification and characterization of a nuclear receptor subfamily I member in the Platyhelminth Schistosoma mansoni (SmNR1)

Wenjie Wu, Edward G. Niles, Hirohisa Hirai, Philip T. LoVerde

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

A cDNA encoding a nuclear receptor subfamily I member in the platyhelminth Schistosoma mansoni (SmNR1) was identified and characterized. SmNR1 cDNA is 2406 bp long and contains an open reading frame encoding a 715 residue protein. Phylogenetic analysis demonstrates that SmNR1 is a divergent member of nuclear receptor subfamily I with no known orthologue. SmNR1 was localized to S. mansoni chromosome 1 by fluorescent in situ hybridization. Gene structure of SmNR1 was determined showing it to consist of eight exons spanning more than 14 kb. Quantitative real-time RT-PCR showed that SmNR1 was expressed throughout schistosome development with a higher expression in eggs, sporocysts and 21-day worms. SmNR1 contains an autonomous transactivation function (AF1) in the A/B domain as demonstrated in a yeast one-hybrid assay; it interacts with SmRXR1 in a yeast two-hybrid assay and in a glutathione S-transferase pull-down assay. Electrophoretic mobility shift assay showed that SmNR1 could form a heterodimer with SmRXR1 to bind to DNA elements containing the half-site AGGTCA, a direct repeat of the half-site separated by 0-5 nucleotides (DR1-DR5) and a palindrome repeat of the half-site not separated by nucleic acids (Pal0). Transient transfection in mammalian COS-7 cells showed that SmNR1/SmRXR1 could enhance the transcriptional activation of a DR2-dependent reporter gene. Our results demonstrate that SmNR1 is a partner of SmRXR1.

Original languageEnglish (US)
Pages (from-to)390-405
Number of pages16
JournalFEBS Journal
Volume274
Issue number2
DOIs
StatePublished - Jan 2007

Keywords

  • Nuclear receptors
  • Schistosoma mansoni
  • SmNR1/SmRXR1 interactions

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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