Hypothetical pathways on glycoRNA biochemistry

Abstract

GlycoRNAs are recently discovered biomolecular structures whose medical relevance is key to understanding cell-cell communication. Research fields such as immunology and tumor research are developing theories around these novel conjugates located on the cell surface. The work of Bertozzi is a reference where the experiments show relevant physicochemical properties of the sialylated RNA conjugates. Going through the current enzymatic and chemical available data, in this work, we hypothesize on the possible biochemical pathways leading to N-glycosylation of RNA nucleobase. Based on the reactivity of glycoRNA with oligosylsaccharide transferases and the PNGase F hydrolase, we base our hypothesis on the conjugation of modified versions of the canonical nucleobases and the GlcNAc moiety through an amide-functionalized small linker. We assume that every nucleobase (A, C, G, and U) is modified following a different enzymatic pathway, but purine bases and pyrimidine bases share the same link to the anomeric carbon of the sugar (Ca), respectively: C7-CONH-Ca and C5-CH2-CONH-Ca.