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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.

The human cytomegalovirus (HCMV) is a ubiquitous, human pathogenic herpesvirus. The complete viral genome is transcriptionally active during infection; however, a large part of its transcriptome has yet to be annotated. In this work, we applied the amplified isoform sequencing technique from Pacific Biosciences to characterize the lytic transcriptome of HCMV strain Towne varS. We developed a pipeline for transcript annotation using long-read sequencing data. We identified 248 transcriptional start sites, 116 transcriptional termination sites and 80 splicing events. Using this information, we have annotated 291 previously undescribed or only partially annotated transcript isoforms, including eight novel antisense transcripts and their isoforms, as well as a novel transcript (RS2) in the short repeat region, partially antisense to RS1. Similarly to other organisms, we discovered a high transcriptional diversity in HCMV, with many transcripts only slightly differing from one another. Comparing our transcriptome profiling results to an earlier ribosome footprint analysis, we have concluded that the majority of the transcripts contain multiple translationally active ORFs, and also that most isoforms contain unique combinations of ORFs. Based on these results, we propose that one important function of this transcriptional diversity may be to provide a regulatory mechanism at the level of translation.

The low-molecular-weight imidazoquinolineamine derivative 1-(2-methyl propyl)-1H-imidazole [4,5-c]quinoline-4-amine (imiquimod) inhibits replication of herpes simplex virus type 2 and cytomegalovirus in infected guinea pigs (6, 24). Imiquimodmediated inhibition of virus replication is related to its ability to induce interferon (IFN). Oral administration of imiquimod induces IFN-␣ in mice, rats, guinea pigs, monkeys, and humans. (New approved nomenclature for IFN genes [9a] is used throughout this paper.) In addition to having antiviral activity, imiquimod was shown to inhibit growth of several transplantable murine tumors, including MC-26 colon carcinoma and Lewis lung carcinoma (71). The induction of IFN-␣ plays a major, but not exclusive, role in this growth inhibition, since an antiserum to mouse IFN-␣ and IFN-␤ significantly reduced the antitumor effect of imiquimod but was not able to abolish it completely.IFN-␣ proteins are represented by a large family of structurally related genes which show about 94% homology at the nucleotide level, while IFN-␤ is encoded by a single gene. IFNA genes are expressed preferentially in cells of lymphoid lineage, and the individual subtypes show cell-type-specific differences in expression (2, 29, 35), while IFNB is expressed in a large variety of cells. The biological significance of the large abundance of IFNA genes is not clear; all IFN-␣ and IFN-␤ subtypes show antiviral and antitumor properties and seem to bind to a common receptor (39); however, some differences between their immunomodulatory effects have been reported (21, 56).Virus-induced expression of IFNA and IFNB genes is mediated by a virus-responsive element (VRE) present in the promoters of IFNA and IFNB genes that, by itself, functions as a virus-specific enhancer and can confer inducibility in infected cells (3,14,19,20,58,65). At least two families of transcriptional factors were shown to play a role in induction of IFN genes that have binding sites within the VRE. One family is the set of IFN-responsive factors IRF-1 and IRF-2, which function as activator and repressor, respectively (22, 23). Overexpression of these two factors can regulate activity of both IFNA and IFNB promoter regions in a transient expression assay; a single nucleotide mutation in the IRF-1 binding site of the murine IFNA4 gene promoter decreased inducibility by about 100-fold (2), and cells expressing IRF-1 antisense mRNA were unable to express IFNB genes (62). However, the role of IRF-1 in induction of the IFN gene has been questioned, since deletion of the IRF-1 gene did not affect virus-mediated inducibility of IFN genes either in mice in vivo or in cultured cells in vitro (53,64). The second family of transcriptional factors are the Bspecific binding proteins that play a role in activation of the IFNB gene (16,19,28,43,77), and recently, a direct role of IFN-induced double-stranded RNA (dsRNA)-dependent kinase in activation of NF-B has been shown (37, 49). Furthermore, it was shown that HMG I(Y) and ATF-2 can bind to the VRE (48...