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J. Biol. Chem., Vol. 280, Issue 25, 24159-24167, June 24, 2005

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Identification and Characterization of a Novel, Psoriasis Susceptibility-related Noncoding RNA gene, PRINS^*

Eniko Sonkoly, Zsuzsanna Bata-Csorgo¶, Andor Pivarcsi, Hilda Polyanka, Anna Kenderessy-Szabo, Gergely Molnar||, Karoly Szentpali**, Lilla Bari, Klara Megyeri, Yvette Mandi, Attila Dobozy, Lajos Kemeny, and Marta Szell

From the Departments of Dermatology and Allergology, ^**Surgery, and Medical Microbiology and Immunobiology, University of Szeged, Szeged 6720 and the Dermatological Research Group and the ^||Institute of Plant Biology, Biological Research Center, Hungarian Academy of Sciences, Szeged 6701, Hungary

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.

Received for publication, February 14, 2005 , and in revised form, April 21, 2005.

^* This work was supported in part by Hungarian Scientific Research Fund Grant TS044826 and National Office of Research and Technology Grant 1A/0012/2002. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ Recipient of the Szechenyi Istvan Fellowship from the Hungarian Ministry of Education.

Supported by the Bolyai Foundation of the Hungarian Academy of Sciences. To whom correspondence should be addressed: Dept. of Dermatology and Allergology, University of Szeged, Korányi fasor 6, Szeged 6720, Hungary. Tel.: 36-62-545-278; Fax: 36-62-545-954; E-mail: szell{at}mail.derma.szote.u-szeged.hu.

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