Conservative sequences in 3′UTR of TCRζ mRNA regulate TCRζ in SLE T cells

Kensei Tsuzaka, Yuka Itami, Chika Kumazawa, Miyuki Suzuki, Yumiko Setoyama, Keiko Yoshimoto, Katsuya Suzuki, Tohru Abe, Tsutomu Takeuchi

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We have demonstrated that T-cell receptor ζ (ζ) mRNA with a 562-bp deleted alternatively spliced 3′-untranslated region (3′UTR) observed in T cells of patients with systemic lupus erythematosus (SLE) can lead to a reduction in ζ and TCR/CD3 (J. Immunol., 2003 & 2005). To determine the region in ζ mRNA 3′UTR for the regulation of ζ, ζ mRNA with 3′UTR truncations ligated into pDON-AI was used to infect murine T-cell hybridoma MA5.8 cells, which do not contain ζ. As a Western blot analysis demonstrated the importance of the regions from +871 to +950, containing conservative sequence 1 (CS1), and +1070 to +1136, containing CS2, for the production of ζ, we constructed MA5.8 mutants carrying ζ mRNA 3′UTR with deletions of these regions (ΔCS1 and ΔCS2 mutants). Western blot and FACS analyses showed significant reduction in the cell surface ζ and TCR/CD3 in both these mutants, and IL-2 production was decreased, compared with MA5.8 cells transfected with wild-type ζ mRNA. Furthermore, real-time PCR demonstrated the instability of ζ mRNA with 3′UTR deletions in these MA5.8 mutants. In conclusion, CS1 and CS2 may be responsible for the regulation of ζ and TCR/CD3 through the stability of ζ mRNA in SLE T cells.

Original languageEnglish
Pages (from-to)311-317
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume367
Issue number2
DOIs
Publication statusPublished - 2008 Mar 7
Externally publishedYes

Keywords

  • 3′UTR
  • Autoimmune disease
  • Conservative sequence
  • IL-2
  • MA5.8 cells
  • Signal transduction
  • Systemic lupus erythematosus
  • T-cell receptor
  • TCRζ
  • mRNA stability

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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