RNASE7 exhibits broad-spectrum activity against Gram-positive and Gram-negative bacteria, fungi, and dermatophytes (Table 1). Its mechanisms include membrane permeabilization and disruption of bacterial cell wall integrity, often targeting lipopolysaccharides (LPS) or outer membrane proteins (e.g., OprI in Pseudomonas aeruginosa) .
RNASE7 bridges innate and adaptive immunity by modulating immune cell responses:
Plasmacytoid Dendritic Cells (pDCs): In combination with self-DNA, RNASE7 triggers robust IFNα production, which protects keratinocytes from herpes simplex virus (HSV-1) infection .
T-Cell Regulation: Reduces Th2 cytokine (IL-4, IL-5, IL-13) production in CD4+ T cells via GATA3 downregulation, independent of RNase activity .
Chemokine Induction: Stimulates keratinocytes to secrete IP-10 (CXCL10) and IFNβ, enhancing antiviral defenses .
RNASE7 levels correlate with susceptibility to infections and inflammatory diseases:
Urinary Tract Infections (UTIs): Children with UTIs exhibit lower urinary RNASE7 concentrations compared to healthy controls. A polymorphism (rs1263872) in RNASE7 reduces bactericidal activity, increasing UTI risk .
Atopic Dermatitis (AD): Impaired RNASE7-mediated Th2 suppression may exacerbate AD pathology .
Therapeutic Potential: Recombinant RNASE7 or strategies to boost endogenous expression (e.g., insulin therapy) are under investigation for antibiotic-resistant infections .
Genetic Variants: The rs1263872 polymorphism (G→C) reduces RNASE7’s bactericidal efficacy, increasing UTI susceptibility in children .
Mechanistic Insights: RNASE7 binds bacterial LPS and membrane proteins, bypassing ribonuclease activity for antimicrobial effects .
Therapeutic Challenges: Overcoming the ribonuclease inhibitor in human skin and optimizing delivery methods for clinical use remain critical hurdles .
Ribonuclease 7 (RNase 7) is a member of the Ribonuclease A superfamily, which consists of structurally similar peptides secreted by immune cells and epithelial tissues. RNase 7 is particularly notable for its potent broad-spectrum antimicrobial activity, making it a significant component of the human innate immune system .
RNase 7 was initially isolated from the stratum corneum, the outermost layer of human skin . This protein exhibited strong ribonuclease activity, contributing to the overall ribonuclease activity observed in human skin. The recombinant form of RNase 7 is typically produced in Escherichia coli (E. coli) and purified using conventional chromatography techniques .
RNase 7 is a cationic peptide, meaning it carries a positive charge, which is crucial for its interaction with negatively charged microbial membranes. The protein consists of 128 amino acids and has a molecular weight of approximately 16.9 kDa . The recombinant version often includes an N-terminal His-tag to facilitate purification and detection .
One of the most remarkable features of RNase 7 is its broad-spectrum antimicrobial activity. It has been shown to be effective against a wide range of pathogenic microorganisms, including bacteria, fungi, and viruses . Notably, RNase 7 exhibits potent activity against vancomycin-resistant Enterococcus faecium, a significant concern in clinical settings due to its resistance to multiple antibiotics .
The antimicrobial activity of RNase 7 is primarily attributed to its ability to degrade RNA within microbial cells. By cleaving RNA, RNase 7 disrupts essential cellular processes, leading to the death of the microorganism . Additionally, its cationic nature allows it to interact with and disrupt microbial membranes, further enhancing its antimicrobial efficacy .
RNase 7 is predominantly expressed in epithelial tissues, including the skin, respiratory tract, and urinary tract . Its expression is regulated by various factors, including microbial presence and inflammatory signals. This regulation ensures that RNase 7 is produced in response to infection, providing a rapid and effective defense mechanism .
Given its potent antimicrobial properties, RNase 7 holds promise as a novel therapeutic agent for treating infections, particularly those caused by antibiotic-resistant bacteria . Further research is needed to fully understand its potential and to develop effective delivery methods for clinical use.