T-cell receptor ζ mRNA with an alternatively spliced 3′ untranslated region is generated predominantly in the peripheral blood T cells of systemic lupus erythematosus patients

Kensei Tsuzaka, Natsuko Onoda, Keiko Yoshimoto, Yumiko Setoyama, Katsuya Suzuki, Ming Pang, Tohru Abe, Tsutomu Takeuchi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

To investigate the mechanism of the downregulation of T-cell receptor ζ chain (TCRζ) expression in the peripheral blood T cells (PBTs) of systemic lupus erythematosus (SLE) patients, we analyzed the 3′ untranslated region (3′UTR) of TCRζ mRNA, because the 3′UTR in mRNA is responsible for posttranscriptional regulation. Use of the reverse transcriptase polymerase chain reaction (RT-PCR) to amplify the 917bp TCRζ 3′UTR cDNA demonstrated that the short variant cDNA (355bp), expressed as an alternatively spliced 3′UTR with 562-bp deletion, was predominated in the PBTs of 11 of 14 SLE patients, whereas mainly the wild-form cDNA (917bp) was detected in the PBTs of seven negative controls (two systemic sclerosis patients, five normal controls) and in two T-cell line hybridomas. Semiquantitative PCR also revealed the predominant expression of the TCRζ mRNA with alternatively spliced 3′UTR (TCRζ mRNA/as-3′UTR), and a decreased expression of TCRζ mRNA with the wild form 3′UTR (TCRζ mRNA/w-3′UTR) in SLE T cells. However, there was no difference in the expression of the open reading frame (ORF) TCRζ mRNA between the negative controls and SLE patients. The TCRζ protein expression level according to Western blot analysis correlated well with that of TCRζ mRNA/w-3′UTR (r = 0.931) and reversibly with TCRζ mRNA/as-3′UTR (r = -0.614), but not with ORF TCRζ mRNA (r = -0.296). It can be concluded that the reduced expression of TCRζ mRNA/w-3′UTR and the pre-dominant expression of TCRζ mRNA/as-3′UTR lead to downregulation of the TCRζ protein in SLE T cells.

Original languageEnglish
Pages (from-to)167-173
Number of pages7
JournalModern Rheumatology
Volume12
Issue number2
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

3' Untranslated Regions
T-Cell Antigen Receptor
Systemic Lupus Erythematosus
Blood Cells
T-Lymphocytes
Messenger RNA
Complementary DNA
Open Reading Frames
Down-Regulation
Systemic Scleroderma
Hybridomas
Reverse Transcriptase Polymerase Chain Reaction
Proteins

Keywords

  • Alternative splicing
  • Autoimmune disease
  • CD3
  • Signal transduction
  • T lymphocytes

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

T-cell receptor ζ mRNA with an alternatively spliced 3′ untranslated region is generated predominantly in the peripheral blood T cells of systemic lupus erythematosus patients. / Tsuzaka, Kensei; Onoda, Natsuko; Yoshimoto, Keiko; Setoyama, Yumiko; Suzuki, Katsuya; Pang, Ming; Abe, Tohru; Takeuchi, Tsutomu.

In: Modern Rheumatology, Vol. 12, No. 2, 2002, p. 167-173.

Research output: Contribution to journalArticle

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abstract = "To investigate the mechanism of the downregulation of T-cell receptor ζ chain (TCRζ) expression in the peripheral blood T cells (PBTs) of systemic lupus erythematosus (SLE) patients, we analyzed the 3′ untranslated region (3′UTR) of TCRζ mRNA, because the 3′UTR in mRNA is responsible for posttranscriptional regulation. Use of the reverse transcriptase polymerase chain reaction (RT-PCR) to amplify the 917bp TCRζ 3′UTR cDNA demonstrated that the short variant cDNA (355bp), expressed as an alternatively spliced 3′UTR with 562-bp deletion, was predominated in the PBTs of 11 of 14 SLE patients, whereas mainly the wild-form cDNA (917bp) was detected in the PBTs of seven negative controls (two systemic sclerosis patients, five normal controls) and in two T-cell line hybridomas. Semiquantitative PCR also revealed the predominant expression of the TCRζ mRNA with alternatively spliced 3′UTR (TCRζ mRNA/as-3′UTR), and a decreased expression of TCRζ mRNA with the wild form 3′UTR (TCRζ mRNA/w-3′UTR) in SLE T cells. However, there was no difference in the expression of the open reading frame (ORF) TCRζ mRNA between the negative controls and SLE patients. The TCRζ protein expression level according to Western blot analysis correlated well with that of TCRζ mRNA/w-3′UTR (r = 0.931) and reversibly with TCRζ mRNA/as-3′UTR (r = -0.614), but not with ORF TCRζ mRNA (r = -0.296). It can be concluded that the reduced expression of TCRζ mRNA/w-3′UTR and the pre-dominant expression of TCRζ mRNA/as-3′UTR lead to downregulation of the TCRζ protein in SLE T cells.",
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AU - Tsuzaka, Kensei

AU - Onoda, Natsuko

AU - Yoshimoto, Keiko

AU - Setoyama, Yumiko

AU - Suzuki, Katsuya

AU - Pang, Ming

AU - Abe, Tohru

AU - Takeuchi, Tsutomu

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AB - To investigate the mechanism of the downregulation of T-cell receptor ζ chain (TCRζ) expression in the peripheral blood T cells (PBTs) of systemic lupus erythematosus (SLE) patients, we analyzed the 3′ untranslated region (3′UTR) of TCRζ mRNA, because the 3′UTR in mRNA is responsible for posttranscriptional regulation. Use of the reverse transcriptase polymerase chain reaction (RT-PCR) to amplify the 917bp TCRζ 3′UTR cDNA demonstrated that the short variant cDNA (355bp), expressed as an alternatively spliced 3′UTR with 562-bp deletion, was predominated in the PBTs of 11 of 14 SLE patients, whereas mainly the wild-form cDNA (917bp) was detected in the PBTs of seven negative controls (two systemic sclerosis patients, five normal controls) and in two T-cell line hybridomas. Semiquantitative PCR also revealed the predominant expression of the TCRζ mRNA with alternatively spliced 3′UTR (TCRζ mRNA/as-3′UTR), and a decreased expression of TCRζ mRNA with the wild form 3′UTR (TCRζ mRNA/w-3′UTR) in SLE T cells. However, there was no difference in the expression of the open reading frame (ORF) TCRζ mRNA between the negative controls and SLE patients. The TCRζ protein expression level according to Western blot analysis correlated well with that of TCRζ mRNA/w-3′UTR (r = 0.931) and reversibly with TCRζ mRNA/as-3′UTR (r = -0.614), but not with ORF TCRζ mRNA (r = -0.296). It can be concluded that the reduced expression of TCRζ mRNA/w-3′UTR and the pre-dominant expression of TCRζ mRNA/as-3′UTR lead to downregulation of the TCRζ protein in SLE T cells.

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