RNase T2 in Inflammation and Cancer: Immunological and Biological Views

Abstract

The RNase T2 family consists of evolutionarily conserved endonucleases that express in many different species, including animals, plants, protozoans, bacteria, and viruses. The main biological roles of these ribonucleases are cleaving or degrading RNA substrates. They preferentially cleave single-stranded RNA molecules between purine and uridine residues to generate two nucleotide fragments with 2'3'-cyclic phosphate adenosine/guanosine terminus and uridine residue, respectively. Accumulating studies have revealed that RNase T2 is critical for the pathophysiology of inflammation and cancer. In this review, we introduce the distribution, structure, and functions of RNase T2, its differential roles in inflammation and cancer, and the perspective for its research and related applications in medicine.

Keywords: RNase T2; cancer; immunity; inflammation; toll-like receptors.

Figure 1

The evolutionary conservation structure of RNase T2 and distribution of RNASET2 in human tissues and immune cells. (A) Amino acid sequence of RNases T2 from human, mouse, rabbit, fruit fly, and classical swine fever virus showing the wide evolutionary conservation of these enzymes. CASI and CASII are indicated in the amino acid sequence, highly conserved AA are indicated as *. (B) Expressions of RNASET2 in human tissues were analyzed in the Human Protein Atlas database, and the resulting transcript expression values, denoted normalized expression (NX), were calculated for each gene in every sample. (C) Expressions of RNASET2 in 18 types of human blood cells and total peripheral blood mononuclear cells (PBMC) were analyzed in the Blood Atlas database. (D) The 3D structure of human RNase T2; the key catalytic residues His 65, His 113, Glu 114, Lys 117, and His 118 are shown in magenta.

Figure 2

An overview of RNase T2 functions in inflammation and cancer. RNase T2 is critical for defending against the infection of exogenous pathogens. RNase T2 is secreted by granulocytes to recruit macrophages and trigger the innate immune response during pathogen infection. RNase T2 has antitumorigenic activity through promoting cancer cell apoptosis, inhibiting angiogenesis, and enhancing antitumor immunity.

Figure 3

Genetic alterations of RNASET2 in human cancers. Frequency of RNASET2 genetic alterations in human tumors from the Cancer Genome Atlas (TCGA) database. Types of alterations include amplification, deep deletion, and mutations.