Pseudouridine residues as substrates for serum ribonucleases.

ABSTRACT: In clinical uses, RNA must maintain its integrity in serum that contains ribonucleases (RNases), especially RNase 1, which is a human homolog of RNase A. These omnipresent enzymes catalyze the cleavage of the P-O^5″ bond on the 3' side of pyrimidine residues. Pseudouridine (Ψ) is the most abundant modified nucleoside in natural RNA. The substitution of uridine (U) with Ψ or N ¹-methylpseudouridine (m¹Ψ) reduces the immunogenicity of mRNA and increases ribosomal translation, and these modified nucleosides are key components of RNA-based vaccines. Here, we assessed the ability of RNase A and RNase 1 to catalyze the cleavage of the P-O^5″ bond on the 3' side of Ψ and m¹Ψ. We find that these enzymes catalyze the cleavage of UpA up to

SUBMITTER: Gutierrez CS 

PROVIDER: S-EPMC12530130 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature