Synthesis of 4-thiouridines with prodrug functionalization for RNA metabolic labeling.

ABSTRACT: Metabolic labeling has emerged as a powerful tool to endow RNA with reactive handles allowing for subsequent chemical derivatization and processing. Recently, thiolated nucleosides, such as 4-thiouridine (4sU), have attracted great interest in metabolic labeling-based RNA sequencing approaches (TUC-seq, SLAM-seq, TimeLapse-seq) to study cellular RNA expression and decay dynamics. For these and other applications (e.g. PAR-CLIP), thus far only the naked nucleoside 4sU has been applied. Here we examined the concept of derivatizing 4sU into a 5'-monophosphate prodrug that would allow for cell permeation and potentially improve labeling efficiency by bypassing the rate-limiting first step of 5' phosphorylation of the nucleoside into the ultimately bioactive 4sU triphosphate (4sUTP). To

SUBMITTER: Moreno S 

PROVIDER: S-EPMC8985182 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature