TET1-Mediated Oxidation of 5-Formylcytosine (5fC) to 5-Carboxycytosine (5caC) in RNA

Maria Basanta-Sanchez; Rui Wang; Zhenzhen Liu; Xiaohan Ye; Minyong Li; Xiaodong Shi; Paul F Agris; Yubin Zhou; Yun Huang; Jia Sheng

doi:10.1002/cbic.201600328

TET1-Mediated Oxidation of 5-Formylcytosine (5fC) to 5-Carboxycytosine (5caC) in RNA

Chembiochem. 2017 Jan 3;18(1):72-76. doi: 10.1002/cbic.201600328. Epub 2016 Nov 22.

Authors

Affiliations

¹ Department of Chemistry, The RNA Institute, University at Albany, State University of New York, 1400 Washington Ave., Albany, NY, 12222, USA.
² Institute of Biosciences and Technology, Texas A&M Health Science Center, 2121 W. Holcombe Blvd, Houston, TX, 77030, USA.
³ Department of Chemistry, University of South Florida, 4202 E. Fowler Ave., Tampa, FL, 33620, USA.
⁴ School of Pharmacy, Shandong University, 44 Wenhua Road W., Jinan, Shandong, 250012, China.

PMID: 27805801
DOI: 10.1002/cbic.201600328

Abstract

It was recently revealed that 5-methylcytosine (5mC) in mRNA, similar to its behavior in DNA, can be oxidized to produce 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC), implying the potential regulatory roles of this post-transcriptional RNA modification. In this study, we demonstrate the in vitro oxidation of 5fC to 5-carboxycytidine (5caC) by the catalytic domain of mammalian ten-eleven translocation enzyme (TET1) in different RNA contexts. We observed that this oxidation process has very low sequence dependence and can take place in single-stranded, double-stranded, or hairpin forms of RNA sequences, although the overall conversion yields are low.

Keywords: 5-carboxycytidine; 5-formylcytidine; 5-methylcytidine; RNA; TET enzyme.

MeSH terms

5-Methylcytosine / chemistry
5-Methylcytosine / metabolism
Base Sequence
Biocatalysis
Catalytic Domain
Chromatography, High Pressure Liquid
Cytosine / analogs & derivatives*
Cytosine / analysis
Cytosine / chemistry
Cytosine / metabolism
Humans
Mixed Function Oxygenases / chemistry
Mixed Function Oxygenases / genetics
Mixed Function Oxygenases / metabolism*
Oxidation-Reduction
Proto-Oncogene Proteins / chemistry
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
RNA / analysis
RNA / metabolism*
Recombinant Proteins / biosynthesis
Recombinant Proteins / chemistry
Recombinant Proteins / isolation & purification
Tandem Mass Spectrometry

Substances

5-formylcytosine
Proto-Oncogene Proteins
Recombinant Proteins
RNA
5-Methylcytosine
5-carboxycytosine
Cytosine
Mixed Function Oxygenases
TET1 protein, human