A Chemical Signature for Cytidine Acetylation in RNA

• DOI: 10.1021/jacs.8b06636
• Publication Date: 2018-09-25T16:02:40Z
• Authors: Justin M. Thomas; Chloe A. Briney; Kellie D. Nance; Jeffrey E. Lopez; Abigail L. Thorpe; Stephen D. Fox; Marie-Line Bortol...; Aldema Sas-Chen; Daniel Arango; Shalini Oberdoerffer; Jerome Cavaille; Thorkell Andresson; Jordan L. Meier
• Keywords: Cytidine; Acetyltransferases; Nucleobase; Borohydride; ribosome biogenesis

N4-acetylcytidine (ac4C) is a highly conserved modified RNA nucleobase whose formation catalyzed by the disease-associated N-acetyltransferase 10 (NAT10). Here we report sensitive chemical method to localize ac4C in RNA. Specifically, characterize susceptibility of borohydride-based reduction and show this reaction can cause introduction noncognate base pairs during reverse transcription (RT). Combining borohydride-dependent misincorporation with ac4C's known base-sensitivity provides unique signature for nucleobase. We reactivity be used quantitatively analyze cellular acetylation, study adapters responsible targeting, probe timing acetylation ribosome biogenesis. Overall, our studies provide foundation defining an expanding landscape cytidine acetyltransferase activity its impact on biology disease.