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

doi:10.1021/jacs.8b06636

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^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

69 Scopus citations

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 language	English (US)
Pages (from-to)	12667-12670
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	140
Issue number	40
DOIs	https://doi.org/10.1021/jacs.8b06636
State	Published - Oct 10 2018

Funding

This work was supported by the National Cancer Institute, Center for Cancer Research (ZIA BC011488-04). This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E.

ASJC Scopus subject areas

General Chemistry
Biochemistry
Catalysis
Colloid and Surface Chemistry

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title = "A Chemical Signature for Cytidine Acetylation in RNA",

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.",

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

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year = "2018",

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T1 - A Chemical Signature for Cytidine Acetylation in RNA

AU - Thomas, Justin M.

AU - Briney, Chloe A.

AU - Nance, Kellie D.

AU - Lopez, Jeffrey E.

AU - Thorpe, Abigail L.

AU - Fox, Stephen D.

AU - Bortolin-Cavaille, Marie Line

AU - Sas-Chen, Aldema

AU - Arango, Daniel

AU - Oberdoerffer, Shalini

AU - Cavaille, Jerome

AU - Andresson, Thorkell

AU - Meier, Jordan L.

N1 - Funding Information: This work was supported by the National Cancer Institute, Center for Cancer Research (ZIA BC011488-04). This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. Publisher Copyright: Copyright © 2018 American Chemical Society.

PY - 2018/10/10

Y1 - 2018/10/10

N2 - 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.

AB - 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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A Chemical Signature for Cytidine Acetylation in RNA

Abstract

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