Site-Specific Synthesis of <i>N</i>⁴-Acetylcytidine in RNA Reveals Physiological Duplex Stabilization.

ABSTRACT: N⁴-Acetylcytidine (ac4C) is a post-transcriptional modification of RNA that is conserved across all domains of life. All characterized sites of ac4C in eukaryotic RNA occur in the central nucleotide of a 5'-CCG-3' consensus sequence. However, the thermodynamic consequences of cytidine acetylation in this context have never been assessed due to its challenging synthesis. Here, we report the synthesis and biophysical characterization of ac4C in its endogenous eukaryotic sequence context. First, we develop a synthetic route to homogeneous RNAs containing electrophilic acetyl groups. Next, we use thermal denaturation to interrogate the biochemical effects of ac4C on duplex stability and mismatch discrimination in a native sequence found in human rRNA. Finally, we demonstrate

SUBMITTER: Bartee D 

PROVIDER: S-EPMC11583671 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature