title: Base pairing and structural insights into the 5-formylcytosine in RNA duplex.
abstract: 5-Formylcytidine (f(5)C), a previously discovered natural nucleotide in the mitochondrial tRNA of many species including human, has been recently detected as the oxidative product of 5-methylcytidine (m(5)C) through 5-hydroxymethylcytidine (hm(5)C) in total RNA of mammalian cells. The discovery indicated that these cytosine derivatives in RNA might also play important epigenetic roles similar as in DNA, which has been intensively investigated in the past few years. In this paper, we studied the base pairing specificity of f(5)C in different RNA duplex contexts. We found that the 5-formyl group could increase duplex thermal stability and enhance base pairing specificity. We present three high-resolution crystal structures of an octamer RNA duplex [5'-GUA(f(5)C)GUAC-3']2 that have been solved under three crystallization conditions with different buffers and pH values. Our results showed that the 5-formyl group is located in the same plane as the cytosine base and forms an intra-residue hydrogen bond with the amino group in the N4 position. In addition, this modification increases the base stacking between the f(5)C and the neighboring bases while not causing significant global and local structure perturbations. This work provides insights into the effects of 5-formylcytosine on RNA duplex.
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Synchrotron Radiation Research Section, MCL National Cancer Institute, Argonne National Laboratory, Argonne, IL, 60439, USA.
authors.forename: Zhipu
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Dharmacon, GE Healthcare, Lafayette, CO 80026, USA.
authors.forename: Kaizhang
authors.initials: K
authors.lastname: He
authors.affiliation: Dharmacon, GE Healthcare, Lafayette, CO 80026, USA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Delaney
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA.
authors.forename: Doris
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, Albany, NY 12222, USA The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA jsheng@albany.edu.
authors.forename: Jia
authors.initials: J
authors.lastname: Sheng
mesh_terms: D020029:Base Pairing; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D012330:RNA, Double-Stranded / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: C560973:5-formylcytosine; D012330:RNA, Double-Stranded; D003596:Cytosine