Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS
Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS
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DOI：
10.1074/jbc.m501704200
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发表时间：
2005-06-24
影响因子：
4.8
通讯作者：
Szell, M
中科院分区：
文献类型：
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作者：
Sonkoly, E;Bata-Csorgo, Z;Szell, M
为了确定导致银屑病易感性的遗传因素，比较了银屑病患者未受累表皮和健康个体表皮的基因表达谱。除了已经表征的基因之外，我们还鉴定了一个具有未知功能的 cDNA，我们对其进行了进一步表征并命名为 PRINS（压力诱导的银屑病易感性相关 RNA 基因）。计算机结构和同源性研究表明 PRINS 可能具有非编码 RNA 的功能。 PRINS含有两个Alu元件，由RNA聚合酶II转录，在人体各种组织中以不同水平表达。实时逆转录-PCR 分析显示，与银屑病病变和健康表皮相比，PRINS 在银屑病患者未受累表皮中表达较高，表明 PRINS 在银屑病易感性中发挥作用。 PRINS 受角质形成细胞的增殖和分化状态调节。 T 淋巴因子（已知会引发银屑病症状）治疗会降低未受累银屑病患者的 PRINS 表达，但不会降低健康表皮中的 PRINS 表达。实时逆转录PCR分析表明，紫外线B照射、病毒感染（单纯疱疹病毒）和翻译抑制等应激信号增加了PRINS的RNA水平。通过 RNA 干扰对 PRINS 进行基因特异性沉默，结果表明 PRINS 的下调会损害血清饥饿后的细胞活力，但在正常血清条件下不会损害细胞活力。我们的研究结果表明 PRINS 作为非编码调节 RNA 起作用，在暴露于压力的细胞中发挥保护作用。此外，表皮中 PRINS 表达升高可能导致银屑病易感性。
To identify genetic factors contributing to psoriasis susceptibility, gene expression profiles of uninvolved epidermis from psoriatic patients and epidermis from healthy individuals were compared. Besides already characterized genes, we identified a cDNA with yet unknown functions, which we further characterized and named PRINS ( Psoriasis susceptibility-related RNA Gene Induced by Stress). In silico structural and homology studies suggested that PRINS may function as a noncoding RNA. PRINS harbors two Alu elements, it is transcribed by RNA polymerase II, and it is expressed at different levels in various human tissues. Real time reverse transcription-PCR analysis showed that PRINS was expressed higher in the uninvolved epidermis of psoriatic patients compared with both psoriatic lesional and healthy epidermis, suggesting a role for PRINS in psoriasis susceptibility. PRINS is regulated by the proliferation and differentiation state of keratinocytes. Treatment with T-lymphokines, known to precipitate psoriatic symptoms, decreased PRINS expression in the uninvolved psoriatic but not in healthy epidermis. Real time reverse transcription-PCR analysis showed that stress signals such as ultraviolet-B irradiation, viral infection ( herpes simplex virus), and translational inhibition increased the RNA level of PRINS. Gene-specific silencing of PRINS by RNA interference revealed that down-regulation of PRINS impairs cell viability after serum starvation but not under normal serum conditions. Our findings suggest that PRINS functions as a noncoding regulatory RNA, playing a protective role in cells exposed to stress. Furthermore, elevated PRINS expression in the epidermis may contribute to psoriasis susceptibility.