A Chemical Signature for Cytidine Acetylation in RNA

Justin M. Thomas, Chloe A. Briney, Kellie D. Nance, Jeffrey E. Lopez, Abigail L. Thorpe, Stephen D. Fox, Marie Line Bortolin-Cavaille, Aldema Sas-Chen, Daniel Arango, Shalini Oberdoerffer, Jerome Cavaille, Thorkell Andresson, Jordan L. Meier

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)12667-12670
Number of pages4
JournalJournal of the American Chemical Society
Volume140
Issue number40
DOIs
StatePublished - 10 Oct 2018
Externally publishedYes

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