Biology subjects

Aharoni, R.

Publications and source records attributed to Aharoni, R..

9 recordsLinked to original sources

bioRxiv2025

An ancient anthozoan protein reveals an alternative evolutionary path of antiviral signaling

How antiviral immunity first arose in animals is a central question in evolutionary biology. Using the sea anemone Nematostella vectensis, we identify CARDIB, a previously uncharacterized gene located next to RLRb, a cnidarian homolog of the vertebrate RIG-I-like receptor family. This conserved genomic linkage across Anthozoa reveals an ancient coupling between immune sensing and regulation. Despite sequence similarity to vertebrate MAVS, CARDIB performs an opposing function: it represses immune genes under basal conditions yet is essential for activation upon viral challenge. CARDIB binds RLRb via a single CARD domain, forming a repressive complex. Loss of either gene abolishes antiviral transcription, disrupts apoptosis, and elevates viral load under lab conditions. Both genes as well as the RLRb paralog, RLRa, are essential for antiviral defense under native conditions. Phylogeny places the cnidarian CARDs distinctly from the vertebrate RLR-MAVS families, revealing an ancient antiviral system regulating antiviral response through CARD-based signaling.

evolutionary biology↗

bioRxiv2025

Characterization of RNA interference in the model cnidarian Nematostella vectensis reveals partial target silencing but lack of small RNA amplification

RNA interference (RNAi) is a sequence-specific mRNA degradation mechanism, which serves as an antiviral pathway by processing viral double-stranded RNA (dsRNA) into short interfering RNAs (siRNAs), leading to virus destruction. It is considered as an ancestral mechanism which invertebrates rely on for defense against viruses, whereas vertebrates have evolved instead the interferon pathway. Recent studies suggest that sea anemones, members of the basally-branching phylum Cnidaria, might possess an immune response with more vertebrate characteristics than previously thought; however, it is unknown whether cnidarians also employ RNAi as an antiviral response similarly to nematodes and insects. Here, we characterize the response of the model cnidarian Nematostella vectensis to simulated viral infection. We injected dsRNA with eGFP sequence into eGFP-expressing transgenic zygotes and show that siRNAs mapping to the eGFP sequence are generated and induce a moderate but significant knockdown of eGFP expression. Interestingly, we detected no evidence for secondary siRNA production, despite their crucial role in the amplification of antiviral response in other organisms. Notably, siRNA pathway components are specifically upregulated upon dsRNA injection, while microRNA pathway components are downregulated. Furthermore, injection of mRNA coding for self-replicating viral gene fused to eGFP, also induced upregulation of siRNA-related genes and a mild decrease in transgene expression. Overall, we propose that N. vectensis possesses an siRNA-mediated antiviral response that lacks secondary amplification and functions as a short-term antiviral mechanism.

evolutionary biology↗

bioRxiv2024

Heat stress drives rapid viral and antiviral innate immunity activation in Hexacorallia

The cnidarian class Hexacorallia, encompassing stony corals and sea anemones, plays a critical role in marine ecosystems. Coral bleaching, the disruption of the symbiosis between stony corals and zooxanthellate algae, is driven by climate change-induced seawater warming and further exacerbated by pathogenic microbes. However, how pathogens, especially viruses, contribute to accelerated bleaching remains poorly understood. The present study utilizes the model sea anemone Nematostella vectensis to explore these dynamics by creating a transgenic line with a reporter gene regulated by sequences from two RIG-I-like receptor (RLR) genes involved in antiviral responses. Under heat stress, the reporter gene showed significant upregulation, indicating that these regulatory sequences are indeed responsive to thermal stress. Analyses of transcriptome data of N. vectensis, Exaiptasia diaphana (another sea anemone), and the stony coral Stylophora pistillata revealed stress-induced activation of a set of bona fide immune-related genes conserved between the three species. Population-specific differences in stress-induced transcriptional responses of immune-related genes were evident in both Nematostella and Stylophora, depending on geographic origin. In Exaiptasia, the presence or absence of zooxanthellae also influenced stress-induced immune gene expression. To test whether the viruses themselves may contribute to this immune response under stress, we subjected Nematostella polyps to variable periods of heat stress and measured the transcript levels of resident viruses as well as selected antiviral genes. While the antiviral genes responded within 1-3 hours of heat stress, viral gene expression was already upregulated within 30 minutes, suggesting that their increase might be contributing to the elevated immune response under stress, and consequentially, the further demise of organismal homeostasis. These findings highlight the complex interplay between environmental stress, viruses, immune responses, and symbiotic states in Hexacorallia. Better understanding of these mechanisms could provide insights into the role of immune pathways in coral resilience and bleaching in a changing climate.

evolutionary biology↗

bioRxiv2023

Venom tradeoff shapes interspecific interactions, physiology and reproduction

The ability of an animal to effectively capture prey and defend against predators is pivotal for its survival. Venom, a mixture of many toxin proteins, shapes predator-prey interactions. Here, we use the sea anemone Nematostella vectensis to test how toxin genotypes impact predator-prey interactions. We developed a new genetic manipulation tool which significantly reduces both RNA and protein levels of Nv1, a major neurotoxin. In concert we recently discovered a native population of Nematostella that has lost Nv1.We demonstrate that these anemones lacking Nv1, have reduced ability to defend themselves against grass shrimp, a native predator. Additionally, secreted Nv1 can act indirectly in defense by attracting mummichog fish, which are known to prey on grass shrimp. This unravels a tritrophic interaction acting in animal defense at the molecular level. Additionally, our work reveals an evolutionary tradeoff, as the reduction of Nv1 levels causes faster growth and increased sexual and asexual reproductive rates.

evolutionary biology↗

bioRxiv2022

Functional analysis in a model sea anemone reveals phylogenetic complexity and a role in cnidocyte discharge of DEG/ENaC ion channels

Ion channels of the DEG/ENaC family share a similar structure but serve strikingly diverse biological functions, such as Na+ reabsorption, mechanosensing, proton-sensing, chemosensing and cell-cell communication via neuropeptides. This functional diversity raises the question of the ancient function of DEG/ENaCs. Using an extensive phylogenetic analysis across many different animal groups, we found a surprising diversity of DEG/ENaCs already in Cnidaria (corals, sea anemones, hyrdoids and jellyfish). Using a combination of gene expression analysis, electrophysiological and functional studies combined with pharmacological inhibition as well as genetic knockout in the model cnidarian Nematostella vectensis, we reveal an unanticipated role for a proton-sensitive DEG/ENaC in discharge of N. vectensis cnidocytes, the stinging cells typifying all cnidarians. Our study supports the view that DEG/ENaCs are versatile channels that have been co-opted for diverse functions since their early occurrence in animals and that respond to simple and ancient stimuli, such as omnipresent protons. TeaserThe analysis of an ion channel class in a sea anemone reveals its role in acidity-induced discharge of stinging cells.

evolutionary biology↗

bioRxiv2020

Functional characterization of the cnidarian antiviral immune response reveals ancestral complexity

Animals developed a broad repertoire of innate immune sensors and downstream effector cascades for defense against RNA viruses. Yet, this system highly varies between different bilaterian animals, masking its ancestral state. In this study we aimed to characterize the antiviral immune response of the cnidarian Nematostella vectensis and decipher the function of the retinoic acid-inducible gene I-like receptors (RLRs) known to detect viral double-stranded RNA (dsRNA) in bilaterians, but activate different antiviral pathways in vertebrates and nematodes. We show that a mimic of long viral dsRNA triggers a complex antiviral immune response bearing features distinctive for both vertebrate and invertebrate systems. Furthermore, the results of affinity assays and knockdown experiments provide functional evidence for the conserved role of RLRs in initiating immune response to dsRNA that originated before the cnidarian-bilaterian split and lay a strong foundation for future research on the evolution of the immune responses to RNA viruses.

evolutionary biology↗

bioRxiv2020

Population Specific Adaptations in Venom Production to Abiotic Stressors in a Widely Distributed Cnidarian

Nematostella vectensis is a sea anemone (Actiniaria, Cnidaria) inhabiting estuaries over a broad geographic range where environmental conditions such as temperatures and salinity vary widely. In cnidarians, antagonistic interactions with predators and prey are mediated by their venom, which may be metabolically expensive. In this study, we challenged Nematostella polyps with heat, salinity, UV light stressors and a combination of all three to determine how abiotic stressors impact toxin expression for individuals collected across this species range. Transcriptomics and proteomics revealed that the highly abundant toxin Nv1 was the most downregulated gene under heat stress conditions in multiple populations. Physiological measurements demonstrated that venom is metabolically costly to produce suggesting that downregulating venom expression under stressful conditions may be advantageous. Strikingly, under a range of abiotic stressors, individuals from different geographic locations along this latitudinal cline modulate venom production levels differently in a pattern reflecting local adaptation.

evolutionary biology↗

bioRxiv2020

Unravelling the developmental and functional significance of an ancient Argonaute duplication

microRNAs (miRNAs), base-pair to messenger RNA targets and guide Argonaute proteins to mediate their silencing. This target regulation is considered crucial for animal physiology and development. However, this notion is based exclusively on studies in bilaterians, which comprise almost all lab model animals. To fill this glaring phylogenetic gap, we characterized the functions of two Argonaute paralogs in the sea anemone Nematostella vectensis of the phylum Cnidaria, which is separated from bilaterians by [~]600 million years. Using genetic manipulation, Argonaute-immunoprecipitations and high-throughput sequencing we provide experimental evidence for the developmental importance of miRNAs in a non-bilaterian animal. Additionally, we uncover unexpected differential distribution of distinct miRNAs between the two Argonautes and the ability of one of them to load additional types of small RNAs. This enables us to postulate a novel model for evolution of miRNA precursors in sea anemones and their relatives, revealing alternative trajectories for metazoan miRNA evolution.

evolutionary biology↗

bioRxiv2017

Cell type-specific expression profiling sheds light on the development of a peculiar neuron, housing a complex organelle

Specialized neurons called cnidocytes define the phylum Cnidaria. They possess an explosive organelle called cnidocyst that is important for prey capture and antipredator defense. An extraordinary morphological and functional complexity of the cnidocysts has inspired numerous studies to investigate their structure and development. However, the transcriptomes of the cells bearing these unique organelles are yet to be characterized, impeding our understanding of the genetic basis of their biogenesis. By generating transgenic lines of the sea anemone Nematostella vectensis using the CRISPR/Cas9 system, we have characterized cell-type specific transcriptomic profiles of various stages of cnidocyte maturation and show that nematogenesis (the formation of functional cnidocysts) is underpinned by dramatic shifts in the spatiotemporal gene expression. We also highlight the stark fall in transcriptional-levels of toxin and structural protein coding genes within cnidocytes with the maturation of capsule. We further reveal that the majority of upregulated genes and enriched biochemical pathways specific to cnidocytes are yet to be characterized. Finally, we unravel the recruitment of a metazoan stress-related transcription factor complex into nematogenesis and highlight its role in the formation of a structural protein of the cnidocyst wall. Thus, we provide novel insights into the biology, development, and evolution of cnidocytes.

evolutionary biology↗