A Chemical Signature for Cytidine Acetylation in RNA

0301 basic medicine 0303 health sciences 03 medical and health sciences Base Sequence RNA, Ribosomal Humans Nucleic Acid Conformation RNA Acetylation Cytidine Oxidation-Reduction
DOI: 10.1021/jacs.8b06636 Publication Date: 2018-09-25T16:02:40Z
ABSTRACT
N4-acetylcytidine (ac4C) is a highly conserved modified RNA nucleobase whose formation is catalyzed by the disease-associated N-acetyltransferase 10 (NAT10). Here we report a sensitive chemical method to localize ac4C in RNA. Specifically, we characterize the susceptibility of ac4C to borohydride-based reduction and show this reaction can cause introduction of noncognate base pairs during reverse transcription (RT). Combining borohydride-dependent misincorporation with ac4C's known base-sensitivity provides a unique chemical signature for this modified nucleobase. We show this unique reactivity can be used to quantitatively analyze cellular RNA acetylation, study adapters responsible for ac4C targeting, and probe the timing of RNA acetylation during ribosome biogenesis. Overall, our studies provide a chemical foundation for defining an expanding landscape of cytidine acetyltransferase activity and its impact on biology and disease.
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