ZUGC-RNA degradation generates immunosuppressor to evade immune responses in eukaryotes.

ABSTRACT: Among the hundreds of modified nucleosides identified in terrestrial life, 2-amino-6-aminopurine (Z) is widely recognized as a prominent modified purine. Recently, RNA written with the ZUGC alphabet shows significant potential in RNA therapeutics as a synthetic biosystem. Here, we demonstrate that ZUGC-RNA can evade immune recognition in eukaryotes, independent of factors such as RNA length, sequence, 5'-triphosphate, modified uridine, and secondary structure. Notably, we discovered that both the degradation of ZUGC-RNA and metabolites of Z-nucleotides can function as immunosuppressors, silencing TLR7 sensing to block immune responses. This mechanism differs from that of pseudo-uridine (Ψ) modified RNA currently in use. ZUGC-RNAs also demonstrate broad applicability across multiple neural

SUBMITTER: Gao S 

PROVIDER: S-EPMC11838226 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature