Human Skin RNases Offer Dual Protection against Invading Bacteria

To control the growth of microorganisms on its surface, human skin produces and releases certain peptides and proteins, including cathelicidin LL-37 and β-defensins. The ribonuclease A (RNase A) superfamily is an important class in this armament (Koczera et al., 2016). This superfamily consists of 13 genes located on chromosome 14; eight of the 13 genes encode proteins (RNases 1–8) that are catalytically active on RNA substrates (Abtin et al. The expression level of RNase 7 is the highest among these four RNases, and only RNases 5 and 7 exhibit antibacterial activity in vitro. The bactericidal action of RNase 7 is based on its binding to and destabilization of the bacterial membrane by way of an electrostatically driven protein-membrane association followed by the formation of transient " holes " on the destabilized membrane, causing the leakage/release of the inner contents (Torrent et al., 2009). RNase 7 exhibits a broad-spectrum activity against a variety of Gram-positive and Gram-negative bacteria including Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and activity is independent of its ribonucleolytic activity (Simanski et al., 2012). The antimicrobial activity of RNase 5 has been observed against the Gram-positive bacterium Streptococcus pneumoniae and the yeast Candida albicans (Hooper et al., 2003). Abtin et al. found that the antifungal activity of RNase 5 against C. albicans requires its ribonucleolytic activity (Abtin et al., 2009; Zasloff, 2009). It is not currently known whether its antibacterial activity against S. pneumoniae requires the same prerequisite/co-requisite. In addition to their antipathogenic activity, the ribonucleolytic activity of RNases on human skin has been investigated. Steve Pascolo's research group discovered that naturally-occurring RNase activity on the surface of human skin specifically targets cytosine (C) residues (Probst et al., 2006). They tested synthetic single-stranded RNA homopolymers 18 nucleotides in length, and determined that while poly(A), poly(G), and poly(U) oligonucleotides remain intact in the presence of human skin RNases, poly(C) oligonucleotides are degraded (Probst et al., 2006). Other human skin proteins also display ribonuclease activity. Miriam Brysk's research group reported that desquamins, glycoproteins not belonging to the RNase A superfamily, have demonstrated both RNase and protease activity (Selvanayagam et al., 1998). Desquamins are expressed in the transition zone between the granular layer and the stratum corneum. Functioning as RNases, desquamins have been found to degrade only poly(C) RNA; homopolymers of A, U, and G are not affected (Selvanayagam et al., 1998). The author experimentally investigates RNA …