2′-O-Methyl-8-methylguanosine as a Z-Form RNA Stabilizer for Structural and Functional Study of Z-RNA

Abstract

In contrast to Z-DNA that was stabilized and well-studied for its structure by chemical approaches, the stabilization and structural study of Z-RNA remains a challenge. In this study, we developed a Z-form RNA stabilizer m8Gm, and demonstrated that incorporation of m8Gm into RNA can markedly stabilize the Z-RNA at low salt conditions. Using the m8Gm-contained Z-RNA, we determined the structure of Z-RNA and investigated the interaction of protein and Z-RNA.

Oligonucleotides DNA containing 8-trifluoromethyl-2′-deoxyguanosine for observing Z-DNA structure

“…The structural model of d(CGC F G CG) 2 is constructed based on the reported Z-form structure and NOE-constrained refining method ( 31 ). The molecular dynamics simulation was carried out in BIOVIA Discovery Studio 4.5 through a standard dynamic cascade with some modifications.…”

Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis

“…Although no antibodies to Z-RNA are currently available, Z-RNA and Z-DNA share very similar structures, and several antisera raised to Z-DNA crossreact with Z-RNA in vitro (Hardin et al, 1987(Hardin et al, , 1988Zarling et al, 1990). To examine if anti-Z-DNA antisera could also detect Z-RNA in cells, we first synthesized a Z-RNA duplex using a newly described approach in which 2 0 -O-methyl-8-methyl modification of guanosine nucleosides (m 8 Gm) allows the stabilization of CG-repeat dsRNA in the Z-conformation (Balasubramaniyam et al, 2018). The introduction of a methyl group at the C8 position strongly favors the syn conformation of guanosine, and modeling this modification in a CG-repeat dsRNA indicates that RNA duplexes containing m 8 Gm can undergo an A / Z transition with energetically favorable dynamics (Figure 3B).…”

“…The introduction of a methyl group at the C8 position strongly favors the syn conformation of guanosine, and modeling this modification in a CG-repeat dsRNA indicates that RNA duplexes containing m 8 Gm can undergo an A / Z transition with energetically favorable dynamics (Figure 3B). In fact, replacing the majority of guanosines with m 8 Gm analogs in CG-repeat dsRNAs produces Z-RNAs that are remarkably stable at physiological salt concentrations in vitro (Balasubramaniyam et al, 2018). We therefore synthesized a hairpin CG-repeat Z-RNA in which most guanosines were modified to m 8 Gm, and, as a control, generated an identical A-RNA hairpin without the m 8 Gm modification (Figure 3C,top).…”

Non-Canonical Helical Structure of Nucleic Acids Containing Base-Modified Nucleotides

“…Sugiyama et al investigated the thermodynamic parameters of DNA B-Z transition for oligonucleotides containing 8-methylguanosine, and reported a reduction in entropic penalty by enthalpic gain during a Z-DNA formation [85]. Later, preferential structures of Z-DNA and RNA were investigated by CD spectra, and fluorescence detection was carried out by an electrophoretic mobility shift assay [86][87][88].…”