Glück, N. | Search bioRxiv

bioRxiv2026

NO VEIN is an ancestral immunity protein involved in plant-virus interaction

The conservation of immune systems from prokaryotes to eukaryotes can guide discovery of immunity genes across the tree of life. Most studies to date have focused on metazoan systems, while the extent of ancestral immunity conservation in plants remains underexplored. Here we show that NO VEIN (NOV), a plant protein previously characterized for its essential developmental roles in Arabidopsis thaliana, shares domain composition and structural similarity with Tiamat, a bacterial antiphage protein. In light of the antiviral function of the bacterial protein, we asked whether NOV is involved in plant-virus interactions. We found that NOV knockdown in the model plant Nicotiana benthamiana resulted in an impaired transcriptional response to tobacco rattle virus, including reduced induction of defense genes, and observed increased potato virus x accumulation in a secondary infection. We also reveal that NOV, previously considered plant-specific, has homologs in animals - pointing to a shared origin. Together, these findings uncover a deeply conserved protein involved in plant-virus interaction, and demonstrate the power of prokaryote-eukaryote homology to reveal new aspects of plant biology.

plant biology↗

bioRxiv2026

Fluorinated RNA origami enables serum-stable nanodevices for sensing and targeting

Chemically modified RNAs with increased stability and reduced immunogenicity have transformed RNA therapeutics. Rational RNA design methods, including RNA origami, seek to further extend RNA medicine and biotechnology by encoding advanced functions such as signalling, targeting, and controlled release within the RNA polymer. However, current design methods lack the ability to integrate chemical modification or predict how it shapes the structure of large RNA assemblies inhibiting its use in RNA therapeutics. Here we demonstrate that 2-fluoro pyrimidine RNA (FY-RNA) origami structures can be co-transcriptionally folded to generate serum-stable nanodevices. Cryogenic electron microscopy reveals that FY-RNA can alter folding pathways and perturb tertiary motifs, while molecular dynamics simulations show how 2-fluoro modification affects hydrogen bonding, sugar pucker, and helix-helix interactions. Despite these structural perturbations, fluorogenic aptamers embedded within RNA origami retain partial activity and enable logic-based molecular sensing in human serum. Finally, we use an FY-RNA scaffold to determine the structure of an FY-RNA anti-Spike aptamer bound to the Spike protein at 3.4 [A] resolution, uncovering fluorine-specific structural motifs and protein interactions. Together, our results establish design principles for nuclease-resistant RNA architectures and position FY-RNA as a versatile polymer for constructing medical nanodevices and environmental sensors. More broadly, this work provides a framework for systematically exploring the folding landscape of chemically modified RNAs, expanding the chemical and functional diversity accessible to nucleic acid nanotechnology and RNA medicine.

biochemistry↗