Translational repression of human matrix metalloproteinases-13 by an alternatively spliced form of T-cell-restricted intracellular antigen-related protein (TIAR)

被引:54
作者
Yu, Q
Cok, SJ
Zeng, CB
Morrison, AR
机构
[1] Washington Univ, Sch Med, Dept Med & Mol Biol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Pharmacol, St Louis, MO 63110 USA
关键词
D O I
10.1074/jbc.M203526200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human matrix metalloproteinases-13 (HMMP13) shows a wide substrate specificity, and its expression is limited to pathological situations such as chronic inflammation and cancer. The coding sequence for HMMP13 is 86% identical to rat matrix metalloproteinases-13 (RMMP13); however, the regulation of HMMP13 and RMMP13 protein synthesis in renal mesangial cells is strikingly different. In human cells there is a discordance between HMMP13 mRNA levels and protein expression. Following IL-1beta or TGF-beta(1) stimulation, HMMP13 mRNA levels increase significantly, whereas the protein expression is absent. This discordance is because of a species-dependent translational repression. In addition to the W-untranslated region of the matrix metalloproteinases-13 (MMP13) gene, the differential expression of an alternatively spliced transcript of the RNA-binding protein TLAR in human cell cultures is also critical for this post-transcriptional regulation. Transient expression of the 17-amino acid insert of the alternatively spliced form of TIAR reverses the HMMP13 mRNA silencing observed in human and primate species. In addition, co-transfection of the alternatively spliced form of TIAR and HMMP13 into Rat2 cells suppresses HMMP13 protein expression. Thus, we report for the first time that a species-dependent TIAR isoform plays a major role in the post-transcriptional silencing for HMMP13.
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页码:1579 / 1584
页数:6
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