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首页> 外文期刊>Biological chemistry >Post-transcriptional regulation of human cathepsin L expression.
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Post-transcriptional regulation of human cathepsin L expression.

机译：人类组织蛋白酶L表达的转录后调控。

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摘要

The expression of cathepsin L, a lysosomal protease, is known to be elevated in cancer and other pathologies. Multiple splice variants of human cathepsin L with variable 5'UTRs exist, which encode for the same protein. Previously we have observed that variant hCATL A (bearing the longest 5'UTR) was translated in vitro with significantly lower efficiency than variant hCATL AIII (bearing the shortest 5'UTR). Contrary to these findings, results of the present study reveal that in cancer cells, hCATL A mRNA exhibits higher translatability in spite of having lower stability than AIII. This is the first report demonstrating a highly contrasting trend in translation efficiencies of hCATL variants in rabbit reticulocytes and live cells. Expression from chimeric mRNAs containing 5'UTRs of A or AIII upstream to luciferase reporter cDNA established the A UTR to be the sole determinant for this effect. Transient transfections of bicistronic plasmids and mRNAs confirmed the presence of a functional Internal Ribosome Entry Site in this UTR. Our data suggest that differential stability and translation initiation modes mediated by the 5'UTRs of human cathepsin L variants are involved in regulating its expression.
机译：组织蛋白酶L（一种溶酶体蛋白酶）的表达在癌症和其他病理学中已知升高。存在具有可变5'UTR的人组织蛋白酶L的多个剪接变体，其编码相同的蛋白质。以前我们已经观察到变异的hCATL A（带有最长的5'UTR）在体外翻译的效率明显低于变异的hCATL AIII（带有最短的5'UTR）。与这些发现相反，本研究的结果表明，在癌细胞中，hCATL A mRNA尽管具有比AIII更低的稳定性，但仍具有较高的可翻译性。这是第一份证明hCATL变体在兔网织红细胞和活细胞中的翻译效率有高度对比趋势的报告。从荧光素酶报道基因上游上游含有A或AIII的5'UTR的嵌合mRNA表达，A UTR是唯一决定这种作用的因素。双顺反子质粒和mRNA的瞬时转染证实了该UTR中存在功能性内部核糖体进入位点。我们的数据表明，由人组织蛋白酶L变体的5'UTR介导的差异稳定性和翻译起始模式参与调节其表达。

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