Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS.
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.
Sonkoly
Eniko
E
Department of Dermatology and Allergology, University of Szeged, Szeged 6720, Hungary.
Bata-Csorgo
Zsuzsanna
Z
Pivarcsi
Andor
A
Polyanka
Hilda
H
Kenderessy-Szabo
Anna
A
Molnar
Gergely
G
Szentpali
Karoly
K
Bari
Lilla
L
Megyeri
Klara
K
Mandi
Yvette
Y
Dobozy
Attila
A
Kemeny
Lajos
L
Szell
Marta
M
D001483:Base Sequence; D015139:Blotting, Southern; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D003001:Cloning, Molecular; D017931:DNA Primers; D004817:Epidermis / Q000378:metabolism; D020868:Gene Silencing; D020022:Genetic Predisposition to Disease; D006801:Humans; D014176:Protein Biosynthesis; D011565:Psoriasis / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C504070:PRINS RNA, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated