The Tautomeric State of -Hydroxycytidine within Base-Paired RNA.

Antiviral nucleoside analogues (e.g., Molnupiravir, Remdesivir) played key roles in the treatment of COVID-19 by targeting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).

Atomic Mutagenesis of -Methyladenosine Reveals Distinct Recognition Modes by Human mA Reader and Eraser Proteins.

-methyladenosine (mA) is an important modified nucleoside in cellular RNA associated with multiple cellular processes and is implicated in diseases. The enzymes associated with the dynamic installation and removal of mA are heavily investigated targets for drug research, which requires detailed knowledge of the recognition modes of mA by proteins. Here, we use atomic mutagenesis of mA to systematically investigate the mechanisms of the two human mA demethylase enzymes FTO and ALKBH5 and the binding modes of YTH reader proteins YTHDF2/DC1/DC2.

A comparative analysis of peptide-delivered antisense antibiotics using diverse nucleotide mimics.

Antisense oligomer (ASO)-based antibiotics that target mRNAs of essential bacterial genes have great potential for counteracting antimicrobial resistance and for precision microbiome editing. To date, the development of such antisense antibiotics has primarily focused on using phosphorodiamidate morpholino (PMO) and peptide nucleic acid (PNA) backbones, largely ignoring the growing number of chemical modalities that have spurred the success of ASO-based human therapy. Here, we directly compare the activities of seven chemically distinct 10mer ASOs, all designed to target the essential gene upon delivery with a KFF-peptide carrier into Our systematic analysis of PNA, PMO, phosphorothioate (PTO)-modified DNA, 2'-methylated RNA (RNA-OMe), 2'-methoxyethylated RNA (RNA-MOE), 2'-fluorinated RNA (RNA-F), and 2'-4'-locked RNA (LNA) is based on a variety of in vitro and in vivo methods to evaluate ASO uptake, target pairing and inhibition of bacterial growth.

Excitonic coupling of RNA-templated merocyanine dimer studied by higher-order transient absorption spectroscopy.

We report the synthesis and spectroscopic analysis of RNA containing the barbituric acid merocyanine rBAM2 as a nucleobase surrogate. Incorporation into RNA strands by solid-phase synthesis leads to fluorescence enhancement compared to the free chromophore. In addition, linear absorption studies show the formation of an excitonically coupled H-type dimer in the hybridized duplex.

Tuning Exciton Coupling of Merocyanine Nucleoside Dimers by RNA, DNA and GNA Double Helix Conformations.

Exciton coupling between two or more chromophores in a specific environment is a key mechanism associated with color tuning and modulation of absorption energies. This concept is well exemplified by natural photosynthetic proteins, and can also be achieved in synthetic nucleic acid nanostructures. Here we report the coupling of barbituric acid merocyanine (BAM) nucleoside analogues and show that exciton coupling can be tuned by the double helix conformation.

Chemoselective labeling and site-specific mapping of 5-formylcytosine as a cellular nucleic acid modification.

DNA methylation has a profound impact on the regulation of gene expression in normal cell development, and aberrant methylation has been recognized as a key factor in the pathogenesis of human diseases such as cancer. The discovery of modified nucleobases arising from 5-methylcytosine (5mC) through consecutive oxidation to give 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) has stimulated intense research efforts regarding the biological functions of these epigenetic marks. This Review focuses on the sensitive detection and quantitation of 5fC in DNA and RNA by chemoselective labeling, which aims at discriminating between 5fC and its thymine counterpart 5-formyluracil (5fU), and summarizes single-base resolution sequencing methods for locus-specific mapping of 5mC and its oxidized derivatives.