Table 2.

Summary of functions, mechanisms, and applications of RNases in diseases

Disease	RNase	Expression during disease	Function	Mechanism of action	Potential applications	Reference
Respiratory tract infection	RNase 2, 3	Upregulated	Inhibit RSV	Ribonuclease activity and other unique ability needed	Biomarker; treatment reagent	(Domachowske et al., 1998a; Domachowske et al., 1998b)
	RNase 5	Unknown	Promote RSV proliferation	By producing 5’tiRNA-GluCTC to inhibit the expression of APOER2	Therapeutic targets	(Wang et al., 2013)
	RNase 3, 6, 7	Upregulated	Anti-bacteria	Inhibit bacteria growth extracellularly; Induce autophagy process in macrophages	Treatment reagent	(Amatngalim et al., 2015; Li et al., 2019)
Skin infection	RNase 1, 4, and 7	Upregulated	Anti-bacteria	Positive charge dependent	Treatment reagent	(Abtin et al., 2009; Harder and Schroder, 2002)
	RNase 5	Unknown	Anti-fungi	Ribonuclease dependent	Treatment reagent	(Abtin et al., 2009)
Intestinal infection	RNase 3	Upregulated	Anti- parasite	Depend on both its cationic nature and enzymatic activity	Treatment reagent	(Amoani et al., 2019)
	Mouse Ang 4 (homolog of RNase 5)	Upregulated	Anti-bacteria	Unknown	Biomarker; treatment reagent	(Walker et al., 2013)
Urinary tract infections	RNase 4, 6, and 7	Upregulated	Anti-bacteria	Positive charge dependent	Biomarker; treatment reagent	(Becknell et al., 2015; Bender et al., 2021; Spencer et al., 2013)
	RNase 3	Upregulated	Anti-parasite	Unknown	Biomarker	(Saxena et al., 2018)
Asthma	RNase 2, 3	Upregulated	Participate in immune responses	Cause tissue damage at the site of inflammation	Biomarker	(Kim et al., 2013)
	RNase 5	Upregulated	Airway remodeling and neo-vascularization	Promote endothelial cells and smooth myocytes proliferation and migration	Biomarker; treatment reagent	(Grzela et al., 2016)
Atopic dermatitis, psoriasis and bullous pemphigoid	RNase 2, 3	Upregulated	Participate in immune responses	Enhance cytokines expression, induce ROS and apoptosis	Biomarker	(Amber et al., 2018; Kim et al., 2017)
	RNase 5	Downregulated in patients with psoriasis	Promote psoriasis progression	Inhibit polymorphonuclear leukocytes degranulation	Biomarker; treatment reagent	(Miyagaki et al., 2012)
	RNase 7	Upregulated	Modulate innate immune	Promote TLR9-mediated self-DNA sensing	Biomarker; treatment reagent	(Kopfnagel et al., 2017; Kopfnagel et al., 2018)
Inflammatory Bowel Disease	RNase 2, 3	Upregulated	Unknown	Unknown	Biomarker	(Liu et al., 2013; Saitoh et al., 1999)
	RNase 5	Downregulated	Inhibit IBD	Maintain gut microbiota, enhance intestinal barrier integrity	Biomarker; treatment reagent	(Bai et al., 2020; Sun et al., 2021)
Sepsis	RNase 1, 3, 7	Upregulated	Attenuate septic cardiomyopathy and cardiac apoptosis	Digest eRNA	Treatment reagent	(Martin et al., 2016; Zechendorf et al., 2020)
Neurological diseases	RNase 2 and 3	Upregulated	Neurotoxicity	Enzymatic activity and the positive charge dependent	Biomarker	(Liu et al., 2013; Rosenberg, 2008a)
	RNase 4 and 5	unknown	Protect neurons	RNase 5 helps motor neuron survival by cutting tRNA into tiRNA	Biomarker; treatment reagent	(Li et al., 2013)
Cancer	RNase 1	Upregulated	Inhibit cancer; promote breast cancer initiation	Kill cancer cells, digest eRNA; bind with EphA4	Biomarker; treatment reagent	(Fischer et al., 2013; Gotte and Menegazzi, 2019)
	RNase 5	Upregulated	Promote cancer growth, survive, and migration	Promote 47S pre-rRNA transcription, product functional tiRNA, bind with PlenxinB2 and EGFR	Biomarker; treatment reagent	(Wang et al., 2018b; Yu et al., 2017)
Cardiovascular disease	RNase 1	Downregulated	Protect cardiovascular system	Digest eRNA	Treatment reagent	(Cabrera-Fuentes et al., 2015; Garnett et al., 2019; Tosar et al., 2021)
	RNase 5	Upregulated	Protect vascular endothelium	Promote endothelial cell proliferation and vesicle tube formation	Biomarker	(Kręcki et al., 2010; Tello-Montoliu et al., 2007)