Epidermal Nucleases. II. The Multiplicity of Ribonucleases in Guinea-Pig Epidermis

Melbye, Susanne W.; Freedberg, Irwin M.

doi:10.1111/1523-1747.ep12494551

Cited by 6 publications

(3 citation statements)

References 17 publications

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“…5, E and F), consistent with previous studies of ex situ mRNA degradation in clinical samples (45). Independent of this process, however, in situ mRNAs from psoriasis lesions are subject to a harsh microenvironment in which endoribonuclease activity may preferentially target longer mRNAs (18,42,53). Short mRNAs, in contrast, may be less often targeted and may indeed be elevated since they can be transcribed more rapidly as part of a coordinated defense response (56,66).…”

Section: Discussionsupporting

confidence: 86%

Integrative RNA-seq and microarray data analysis reveals GC content and gene length biases in the psoriasis transcriptome

Xing

Voorhees

Elder

et al. 2014

Physiological Genomics

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Gene expression profiling of psoriasis has driven research advances and may soon provide the basis for clinical applications. For expression profiling studies, RNA-seq is now a competitive technology, but RNA-seq results may differ from those obtained by microarray. We therefore compared findings obtained by RNA-seq with those from eight microarray studies of psoriasis. RNA-seq and microarray datasets identified similar numbers of differentially expressed genes (DEGs), with certain genes uniquely identified by each technology. Correspondence between platforms and the balance of increased to decreased DEGs was influenced by mRNA abundance, GC content, and gene length. Weakly expressed genes, genes with low GC content, and long genes were all biased toward decreased expression in psoriasis lesions. The strength of these trends differed among array datasets, most likely due to variations in RNA quality. Gene length bias was by far the strongest trend and was evident in all datasets regardless of the expression profiling technology. The effect was due to differences between lesional and uninvolved skin with respect to the genome-wide correlation between gene length and gene expression, which was consistently more negative in psoriasis lesions. These findings demonstrate the complementary nature of RNA-seq and microarray technology and show that integrative analysis of both data types can provide a richer view of the transcriptome than strict reliance on a single method alone. Our results also highlight factors affecting correspondence between technologies, and we have established that gene length is a major determinant of differential expression in psoriasis lesions.

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Section: Discussionsupporting

confidence: 86%

Integrative RNA-seq and microarray data analysis reveals GC content and gene length biases in the psoriasis transcriptome

Xing

Voorhees

Elder

et al. 2014

Physiological Genomics

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“…This result has a great impact on the development of RNA-based drugs. Since a similar specificity was observed for the major ribonuclease extracted from mammalian's epidermis [ 38 , 39 ] we anticipate that the utilization of C-low RNA may be a method to increase the efficacy of RNA-therapies delivered transcutaneously, intradermally or subcutaneously.…”

Section: Discussionmentioning

confidence: 54%

Characterization of the ribonuclease activity on the skin surface

Probst

Brechtel

Scheel

et al. 2006

Genet Vaccines Ther

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The rapid degradation of ribonucleic acids (RNA) by ubiquitous ribonucleases limits the efficacy of new therapies based on RNA molecules. Therefore, our aim was to characterize the natural ribonuclease activities on the skin and in blood plasma i.e. at sites where many drugs in development are applied. On the skin surfaces of Homo sapiens and Mus musculus we observed dominant pyrimidine-specific ribonuclease activity. This activity is not prevented by a cap structure at the 5'-end of messenger RNA (mRNA) and is not primarily of a 5'-or 3'-exonuclease type. Moreover, the ribonuclease activity on the skin or in blood plasma is not inhibited by chemical modifications introduced at the 2'OH group of cytidine or uridine residues. It is, however, inhibited by the ribonuclease inhibitor RNasin ® although not by the ribonuclease inhibitor SUPERase· In™. The application of our findings in the field of medical science may result in an improved efficiency of RNA-based therapies that are currently in development.

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“…The discrepancy between CE maturation and disappearance of nuclei, both of which concomitantly occur during the keratinization process, may be based on a difference in their regulatory mechanisms; CE maturation is largely mediated by TGases (1–3), whereas the disappearance of nuclei upon transition of keratinocytes into the SC is mediated by hydrolyzing enzymes, including ribonucleases and deoxyribonucleases (50–53), though the precise mechanisms underlying the retention of nuclei in parakeratosis are still unclear. In fact, those cases showing discontinuous staining of involucrin even in the same psoriatic plaque (Fig.…”

Section: Discussionmentioning

confidence: 99%

Ratio of immature cornified envelopes does not correlate with parakeratosis in inflammatory skin disorders

Hirao

Terada

Takeuchi

et al. 2003

Experimental Dermatology

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We have previously established a non-invasive method to evaluate the maturity of cornified envelopes (CEs), and have reported the appearance of immature CEs in the stratum corneum (SC) with poor barrier function, such as the SC of the face. The purpose of the present study was to evaluate CEs in inflammatory skin disorders, and to clarify the relationship between the appearance of the immature CEs and parakeratosis, which is often used as a marker for defective keratinization in inflammatory skin disorders. Cornified envelopes in the outermost SC of involved areas of psoriasis vulgaris (PV) and atopic dermatitis (AD) were strikingly heterogeneous, and consisted of immature CEs stained with anti-involucrin and mature CEs stained with Nile red, whereas CEs of the uninvolved areas were relatively homogeneous, exhibiting mature phenotype. The ratio of immature CEs was significantly higher in the involved areas of PV and AD than that in the corresponding uninvolved areas, suggesting that defective CE maturation may, at least in part, account for the inflammatory disorders. Simultaneous evaluation of CE maturity and parakeratosis was carried out by a combination of involucrin immunostaining and nuclear staining of detergent-dissociated corneocytes. In the involved area of PV, four types of corneocytes in regard to the combination of involucrin staining and nuclear remnant were observed, while both immature CEs and parakeratosis were more often detected in the involved areas of PV than in the uninvolved areas or the upper arm of healthy subjects as a normal control. Thus, corneocytes with involucrin-positive immature CEs were not always associated with parakeratosis at the cellular level. In the involved areas of PV, the ratio of immature CEs and that of parakeratosis were heterogeneous, depending on the cases, and no correlation between the ratios was observed. Inter-individual and intraindividual variations in CE maturity were also suggested by the heterogeneous localization of involucrin in the psoriatic epidermis as examined by immunohistochemistry. In addition, in the face of healthy subjects, four types of corneocytes were similarly detected, and the ratio of immature CEs was significantly higher than that of parakeratosis. These results obviously suggest that the maturation of CEs and disappearance of nuclei are differentially regulated in the epidermis.

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Epidermal Nucleases. II. The Multiplicity of Ribonucleases in Guinea-Pig Epidermis

Cited by 6 publications

References 17 publications

Integrative RNA-seq and microarray data analysis reveals GC content and gene length biases in the psoriasis transcriptome

Integrative RNA-seq and microarray data analysis reveals GC content and gene length biases in the psoriasis transcriptome

Characterization of the ribonuclease activity on the skin surface

Ratio of immature cornified envelopes does not correlate with parakeratosis in inflammatory skin disorders

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