The Ribonuclease A Superfamily in Humans: Canonical RNases as the Buttress of Innate Immunity

Abstract

In humans, the ribonuclease A (RNase A) superfamily contains eight different members that have RNase activities, and all of these members are encoded on chromosome 14. The proteins are secreted by a large variety of different tissues and cells; however, a comprehensive understanding of these proteins’ physiological roles is lacking. Different biological effects can be attributed to each protein, including antiviral, antibacterial and antifungal activities as well as cytotoxic effects against host cells and parasites. Different immunomodulatory effects have also been demonstrated. This review summarizes the available data on the human RNase A superfamily and illustrates the significant role of the eight canonical RNases in inflammation and the host defence system against infections.

AIF-1 and RNASET2 Play Complementary Roles in the Innate Immune Response of Medicinal Leech

“…Interestingly, several members of this RNase superfamily are often expressed in different types of immune cells [50]. For instance, EDN/RNase2 and ECP/RNase3 have been detected in the secondary granules of eosinophils [51], whereas Rnase2 and RNase3 represent two actively secreted proteins that were found in the granules of these cells during an inflammatory response [52]. …”

Comparative functional analysis of ribonuclease 1 homologs: molecular insights into evolving vertebrate physiology

“…They are not homologous to any other class of eukaryotic RNases, and together constitute an extensive superfamily of proteins that has been the subject of intense biochemical, structural, and evolutionary studies for over half a century. With compact structures, high stability, and a shared ability to catalyze the non-specific degradation of RNA, these small and hardy enzymes are purported to serve a variety of diverse biological roles in vivo , including supporting host defense and innate immunity [1, 2]. Indeed, numerous phylogenetic reconstructions and other analyses indicate that the family is evolving and expanding rapidly, and that many members are under positive selection for increased functional diversification, as is common with immunity-related protein families [3-6].…”

Pancreatic Ribonuclease

“…The human genome codes for 122 separate ribonucleases. The RNAse A superfamily consists of eight "canonical" ribonucleases with enzymatic activity and structural homology to RNase A (15). All are secretory proteins that share a disulfide bonded tertiary structure and are able to degrade RNA.…”

“…Understanding of their physiological role is incomplete but most are important for host defense and angiogenesis as well as digestion (9). The first member to be described is RNase 1 which in addition to being a pancreatic enzyme is produced in a variety of cells including vascular endothelial cells where after secretion it degrades vascular polymeric RNA and has anti-HIV-1 activity (15). RNase 2 and 3 are eosinophil secretory proteins termed eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) respectively (15).…”

“…The first member to be described is RNase 1 which in addition to being a pancreatic enzyme is produced in a variety of cells including vascular endothelial cells where after secretion it degrades vascular polymeric RNA and has anti-HIV-1 activity (15). RNase 2 and 3 are eosinophil secretory proteins termed eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) respectively (15). RNase 4 is present in multiple tissues but it's physiologic role is unclear.…”