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mRNA with an Alternatively Spliced 3'-Untranslated Region Detected in Systemic Lupus Erythematosus Patients Leads to the Down-Regulation of TCR and TCR/CD3 Complex 1
Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, Saitama, Japan
The reduction or absence of TCR 
-chain () expression in systemic lupus erythematosus (SLE) patients is thought to be related to the pathogenesis of SLE. Recently, we reported the predominant expression of mRNA containing an alternatively spliced 3'-untranslated region (3'UTR; mRNA/as-3'UTR) and a reduction in the expression of mRNA containing the wild-type 3'UTR (mRNA/w-3'UTR) in T cells from SLE patients. Here we show that AS3'UTR mutants (MA5.8 cells deficient in protein that have been transfected with mRNA/as-3'UTR) exhibit a reduction in the expression of TCR/CD3 complex and protein on their cell surface as well as a reduction in the production of IL-2 after stimulation with anti-CD3 Ab compared with that in wild-type 3'UTR mutants (MA5.8 cells transfected with mRNA/w-3'UTR). Furthermore, the real-time PCR analyses demonstrated that the half-life of mRNA/as-3'UTR in AS3'UTR mutants (3 h) was much shorter than that of mRNA/w-3'UTR in wild-type 3'UTR mutants (15 h). Thus, the lower stability of mRNA/as-3'UTR, which is predominant in SLE T cells, may be responsible for the reduced expression of the TCR/CD3 complex, including protein, in SLE T cells.
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