Biology subjects

Ofir, G.

Publications and source records attributed to Ofir, G..

6 recordsLinked to original sources

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↗

bioRxiv2023

The SARM1 TIR domain produces glycocyclic ADPR molecules as minor products

Sterile alpha and TIR motif-containing 1 (SARM1) is a protein involved in programmed death of injured axons. Following axon injury or a drug-induced insult, the TIR domain of SARM1 degrades the essential molecule nicotinamide adenine dinucleotide (NAD+), leading to a form of axonal death called Wallerian degeneration. Degradation of NAD+ by SARM1 is essential for the Wallerian degeneration process, but accumulating evidence suggest that other activities of SARM1, beyond the mere degradation of NAD+, may be necessary for programmed axonal death. In this study we show that the TIR domains of both human and fruit fly SARM1 produce 1''-2' and 1''-3' glycocyclic ADP-ribose (gcADPR) molecules as minor products. As previously reported, we observed that SARM1 TIR domains mostly convert NAD+ to ADPR (for human SARM1) or cADPR (in the case of SARM1 from Drosophila melanogaster). However, we now show that human and Drosophila SARM1 additionally convert [~]0.1-0.5% of NAD+ into gcADPR molecules. We find that SARM1 TIR domains produce gcADPR molecules both when purified in vitro and when expressed in bacterial cells. Given that gcADPR is a second messenger involved in programmed cell death in bacteria and likely in plants, we propose that gcADPR may play a role in SARM1-induced programmed axonal death in animals.

molecular biology↗

bioRxiv2022

Conservation of antiviral systems across domains of life reveals novel immune mechanisms in humans

Viral infection is a common threat to prokaryotic and eukaryotic life, which has resulted in the evolution of a myriad of antiviral systems. Some of these eukaryotic systems are thought to have evolved from prokaryotic antiphage proteins, with which they may display sequence and structural homology. Here, we show that homologs of recently discovered antiphage systems are widespread in eukaryotes. We demonstrate that such homologs can retain a function in immunity by unveiling that eukaryotic proteins of the anti-transposon piRNA pathway display domain homology with the antiphage system Mokosh. We further utilise this conservation to discover novel human antiviral genes related to the Eleos and Lamassu prokaryotic systems. We propose that comparative immunology across domains of life can be leveraged to discover immune genes in eukaryotes.

genomics↗

bioRxiv2022

An expanding arsenal of immune systems that protect bacteria from phages

Bacterial anti-phage defense systems are frequently clustered in microbial genomes, forming defense islands. This genomic property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms in bacteria is still unknown. In this study we report the discovery of 21 new defense systems that protect bacteria from phages, based on computational genomic analyses and phage infection experiments. We find multiple systems with protein domains known to be involved in eukaryotic anti-viral immunity, including ISG15-like proteins, dynamin-like proteins, and SEFIR domains, and show that these domains participate in bacterial defense against phages. Additional systems include protein domains predicted to manipulate DNA and RNA molecules, as well as multiple toxin-antitoxin systems shown here to function in anti-phage defense. The systems we discovered are widely distributed in bacterial and archaeal genomes, and in some bacteria form a considerable fraction of the immune arsenal. Our data substantially expand the known inventory of defense systems utilized by bacteria to counteract phage infection.

microbiology↗

bioRxiv2021

Class I DISARM provides anti-phage and anti-conjugation activity by unmethylated DNA recognition

Bacteriophages impose a strong evolutionary pressure on microbes for the development of mechanisms of survival. Multiple new mechanisms of innate defense have been described recently, with the molecular mechanism of most of them remaining uncharacterized. Here, we show that a Class 1 DISARM (defense island system associated with restriction-modification) system from Serratia sp. provides broad protection from double-stranded DNA phages, and drives a population of single-stranded phages to extinction. We identify that protection is not abolished by deletion of individual DISARM genes and that the absence of methylase genes drmMI and drmMII does not result in autoimmunity. In addition to antiphage activity we also observe that DISARM limits conjugation, and this activity is linked to the number of methylase cognate sites in the plasmid. Overall, we show that Class 1 DISARM provides robust anti-phage and anti-plasmid protection mediated primarily by drmA and drmB, which provide resistance to invading nucleic acids using a mechanism enhanced by the recognition of unmethylated cognate sites of the two methylases drmMI and drmMII.

microbiology↗

bioRxiv2021

Antiviral activity of bacterial TIR domains via signaling molecules that trigger cell death

The Toll/interleukin-1 receptor (TIR) domain is a canonical component of animal and plant immune systems. In plants, intracellular pathogen sensing by immune receptors triggers their TIR domains to generate a molecule which is a variant of cyclic ADP-ribose (v-cADPR). This molecule is hypothesized to activate plant cell death via a yet unresolved pathway. TIR domains were recently also shown to be involved in a bacterial anti-phage defense system called Thoeris, but the mechanism of Thoeris defense remained unknown. In this study we report that phage infection triggers Thoeris TIR-domain proteins to produce an isomer of cyclic ADP-ribose. This molecular signal activates a second protein, ThsA, which then depletes the cell of the essential molecule nicotinamide adenine dinucleotide (NAD) and leads to abortive infection and cell death. We further show that similar to eukaryotic innate immune systems, bacterial TIR-domain proteins determine the immunological specificity to the invading pathogen. Our results describe a new antiviral signaling pathway in bacteria, and suggest that generation of intracellular signaling molecules is an ancient immunological function of TIR domains conserved in both plant and bacterial immunity.

microbiology↗