Biology subjects

Kanevskaya, A.

Publications and source records attributed to Kanevskaya, A..

3 recordsLinked to original sources

bioRxiv2026

A widespread NADase domain links bacterial immunity with human TEP1

Recent discoveries on bacterial immunity have revealed that several protein domains involved in anti-phage defense are conserved in eukaryotes, such as SIRim, TIR, PNP and gasdermin. Bacterial immune systems therefore have the potential to illuminate fundamental biological mechanisms throughout the tree of life. Here, we report that DUF4062 domains - which we rename NIR (NADase in bacterial immunity and vault ribonucleoproteins) - function in bacterial immunity against phages. We first identified NIR as an effector of Avs defense proteins, where it depletes cellular NAD+ to block viral infection. We then show that NIR domains are recurrently found as effectors in diverse defense systems. We use this association to uncover Vulcan and Vesta, two defense systems which trigger NAD+ depletion upon sensing distinct viral signals. Remarkably, NIR domains are widespread in eukaryotes where they are embedded in multiple NLR-like proteins. In particular, we identified a NIR domain with conserved NADase activity in the human TEP1 protein, a component of the telomerase complex and vault ribonucleoproteins. Together, these findings reveal an enzymatic activity shared between bacterial immunity and enigmatic eukaryotic machineries.

microbiology↗

bioRxiv2025

Target-induced Argonaute-HNH filaments confer bacterial immunity

Argonaute proteins provide innate immunity in all domains of life through guide-dependent recognition of invader nucleic acids. While eukaryotic Argonautes (eAgos) act on RNA during RNA interference, prokaryotic Argonautes (pAgos) mainly recognize DNA targets. Many eAgos and some pAgos are active nucleases that directly cleave their targets. In contrast, short pAgos lack the nuclease activity and are co-encoded with additional effectors. Diverse effector domains in short pAgo systems include NADases and tentative nucleases, but their mechanisms of activation remain largely unknown. Here, we characterize SPARHA systems (short prokaryotic argonautes, HNH-associated) encoding HNH nuclease effectors. We show that short pAgo activates the HNH effector after RNA-guided DNA recognition. Target recognition induces formation of filaments of SPARHA with double active sites formed at the interfaces of repetitive HNH domains, which results in indiscriminate collateral degradation of DNA and protects bacterial population from invaders. The results show that pAgos and associated effectors act as modular two-component systems that translate recognition of specific DNA into immune response through assembly of supramolecular complexes, deleterious for invaders and potentially useful for biotechnology.

molecular biology↗

bioRxiv2023

DNA-targeting short Argonaute triggers effector nuclease to protect bacteria from invaders

Two prokaryotic defence systems, Argonautes (pAgos) and CRISPR-Cas, detect invader nucleic acids using complementary guides. Upon recognition, the target is cleaved through nuclease activities of pAgo or Cas proteins thus protecting the cell from invasion. However, not all pAgos are active nucleases. Members of a large clade of short pAgos bind nucleic acid guides but lack nuclease activity suggesting a different mechanism of action. Here, we have investigated short pAgo from Novosphingopyxis baekryungensis (NbaAgo). We have shown that NbaAgo forms a heterodimeric complex, SPARDA, with a co-encoded effector nuclease. RNA-guided target DNA recognition unleashes the nuclease activity of SPARDA leading to indiscriminate collateral cleavage of DNA and RNA. Activation of SPARDA results in cell death during plasmid transformation or phage infection, thus protecting bacterial population from invaders. The collateral activity of SPARDA allows highly sensitive detection of specific DNA targets. SPARDA expands the list of prokaryotic immune systems that elicit suicidal cell response with a unique range of nuclease activities, creating additional opportunities for biotechnologies.

molecular biology↗