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At least 19 recordsLinked to original sources

PubMed2026

RNAi in the Rhizarian Phytopathogen Plasmodiophora brassicae: The Causal Agent of Clubroot Disease in Cruciferous Crops.

Although RNA interference (RNAi) is widespread and functionally important across eukaryotes, RNAi pathways are diverse or even lost in some lineages. Rhizaria represents a major and distinct eukaryotic supergroup that includes Plasmodiophora brassicae (Pb), the causal agent of cruciferous clubroot disease, yet RNAi in this lineage remains poorly understood. Here, we characterized an unusual RNAi pathway in Pb. Small RNA sequencing across five representative Pb life stages revealed abundant siRNAs and miRNAs characterized by a predominant 21-nt length, phased genomic distribution, 2-nt 3' overhangs, and a strong 5'-cytidine bias. Three Pb miRNAs were further validated by northern blotting and stem-loop RT-qPCR. Genome analysis identified two canonical AGO homologs, PbAGO1 and PbAGO2, but no Dicer homologs, except for an RNase III-containing Drosha-like protein, PbDRL. Functional analyses showed that PbAGO1 and PbAGO2 mediate gene silencing, whereas PbDRL is required for sRNA biogenesis. Further, the cell wall component chitin was identified from Pb zoosporangia during the early infection and RNAi interfering with its biosynthesis in transgenic plants of Arabidopsis and Brassica napus blocked Pb early infection and conferred broad-spectrum resistance. Our study uncovers an unusual RNAi pathway in Rhizaria and provides a promising strategy to control cruciferous clubroot disease.

Plasmodiophora brassicae↗

PubMed2026

Exploring the potential of RNA interference (RNAi) in mosquito control: from mechanisms to molecular insights.

Mosquito-borne diseases represent a growing global health crisis, exacerbated by climate change and insecticide resistance. RNA interference (RNAi), a natural mechanism of gene silencing, offers a promising, target-specific alternative for mosquito control. This review explores the potential of RNAi to disrupt critical physiological processes, such as reproduction and disease transmission, thereby reducing vector populations and competence. We examine the mechanisms of RNAi, its application in combatting insecticide resistance, and recent advancements in delivery systems, including nanobody- and chitosan-based nanoparticles, which enhance the stability and uptake of double-stranded RNA (dsRNA) molecules. However, significant challenges remain, such as optimizing field-effective delivery methods and assessing potential off-target effects on non-target organisms. Continued innovation in RNAi technology is pivotal for developing sustainable and environmentally sound vector control strategies. This review synthesizes current research, highlighting the molecular insights, practical applications, and future directions for integrating RNAi into modern public health initiatives.

RNA Interference↗

PubMed2026

Screening, optimization and artificial recombination of dsRNA fragments for RNAi-mediated pest resistance in Apolygus lucorum.

RNA interference (RNAi) is an eco-friendly strategy for pest management, with double-stranded RNA (dsRNA) as the core functional component. In this study, three RNAi target genes (Ubx, wupA and Dpp) with strong lethal effects on Apolygus lucorum were screened via microinjection. The 7-day cumulative mortalities were 56.67 ± 3.33% for dsUbx, 94.44 ± 1.11% for dswupA and 92.22 ± 1.11% for dsDpp. We optimized dsRNA sequences by removing conserved sequences in non-target organisms based on homology alignment and off-target risk analysis. The optimized fragments dswupA-OTE and dsDpp-OTE still exhibited high insecticidal activity, with 7-day cumulative mortalities of 77.78 ± 2.94% and 70.00 ± 1.93%, respectively. We also evaluated the effects of dsRNA length and target sites on RNAi efficiency and screened potent short dsRNA fragments. Novel artificially recombinant dsRNAs were constructed by assembling effective short fragments from different genes, which retained strong insecticidal activity despite shorter sequence length. This study verifies the feasibility of multi-target recombinant dsRNA for pest control and provides a theoretical basis for developing multi-gene RNAi technologies against A. lucorum.

Apolygus lucorum↗

PubMed2026

Comparative evaluation of chitosan-based and star polycation nanocarriers for enhanced RNAi efficacy targeting CmFibL in Cnaphalocrocis medinalis.

BACKGROUND: The rice leaf folder, Cnaphalocrocis medinalis, causes substantial rice yield losses through larval leaf-rolling behavior. RNA interference (RNAi) offers a sustainable alternative, but its application in Lepidoptera is hindered by dsRNA degradation and poor cellular uptake. This study developed nanocarrier-mediated dsRNA delivery to overcome these limitations. RESULTS: Three nanocarriers - chitosan (CS), chitosan-tripolyphosphate (CS-TPP), and star polycation (SPc) - were compared for enhancing RNAi efficiency targeting the C. medinalis fibroin light chain gene (CmFibL). CS-TPP and SPc achieved 61% and 55% silencing efficiency, respectively, representing 2.7-fold improvement over naked dsRNA (23%). All nanocarriers protected dsRNA from RNase A (30 min) and midgut fluid (6 h) degradation. CmFibL knockdown caused severe silk defects, prolonged pupal duration by 23%, reduced pupal weight by 33%, and decreased leaf-rolling damage by 31% in glasshouse cage trials. Transcriptomics revealed down-regulation of amino acid metabolism and activation of endoplasmic reticulum (ER) stress and immune responses. No off-target effects were detected in human genome, nor in any predators or parasitoids sharing the same ecological niche. CONCLUSION: CS-TPP and SPc nanocarriers effectively enhance RNAi efficiency in a Lepidopteran pest. Targeting CmFibL disrupts silk-mediated feeding shelters with minimal ecological risk, providing a practical framework for field application of RNAi-based biopesticides against leaf-rolling rice pests. © 2026 Society of Chemical Industry.

Animals↗

PubMed2026

Chitosan-dsRNA improves tissue stability and delivery for RNAi-mediated Varroa destructor control.

BACKGROUND: Varroa destructor is an ectoparasitic mite and a major threat to honey-bee colony health worldwide. RNA interference (RNAi) offers a potentially species-specific approach for mite control, but practical application is limited by double-stranded RNA (dsRNA) degradation and inefficient delivery to mites. This study evaluated coatomer protein I (COPI) complex subunits as RNAi targets and tested whether chitosan-based dsRNA formulation could improve dsRNA stability, tissue uptake, and delivery from honey-bees to mites. RESULTS: Direct microinjection of dsRNAs targeting COPB, COPD, and COPE significantly reduced target-gene expression and mite survival compared with the double-stranded green fluorescent protein (dsGFP) control, with 72-h survival rates of 8.0%, 12.7%, and 5.3%, respectively, compared with 40.7% in the control group (all log-rank P < 0.0001). Chitosan-conjugated dsRNA remained detectable for longer periods than naked dsRNA in honey-bee tissue fluids, and CNP-Cy3-dsGFP was detected in the honey-bee midgut and fat body. A qualitative fluorescence observation in V. destructor was consistent with host-to-mite dsRNA transfer. Ingestion of COP-targeted chitosan-dsRNAs reduced mite survival, whereas honey-bee survival and expression of honey-bee COP orthologs were not affected. In silico analysis detected no contiguous ≥19-nt matches between Varroa COP dsRNAs and the honey-bee transcriptome or genome. CONCLUSION: COPI subunits are promising RNAi targets in V. destructor, and chitosan formulation may improve dsRNA persistence and uptake while supporting honey-bee-mediated delivery to mites. These laboratory findings support further evaluation of chitosan-formulated dsRNA as a potentially species-selective strategy for Varroa management, while broader safety assessment and field validation remain necessary. © 2026 Society of Chemical Industry.

COPI complex↗

PubMed2025

Generation of Cdc20 RNAi-Sensitive Cell Lines to Study Mitotic Exit.

Accurate mitotic progression ensures the fidelity of genome passage. Cdc20 is a key mitotic regulator. It promotes mitotic exit by activating the anaphase-promoting complex or cyclosome (APC/C) and monitors kinetochore-microtubule attachment through activating the spindle assembly checkpoint (SAC). Precise characterization of Cdc20 requires efficient depletion of endogenous Cdc20, which is extremely difficult to achieve by RNA interference (RNAi). This chapter describes the methodology to generate Cdc20 RNAi-sensitive cell lines with the help of CRISPR/Cas9 technology. These cell lines are highly sensitive to Cdc20 RNAi and provide a very useful tool for Cdc20 functionality investigation without the interference of endogenous Cdc20 protein. Similar strategy could be applied to other genes.

Cdc20 Proteins↗

PubMed2026

De novo transcriptome meta-analysis reveals candidate genes involved in life-stage transitions for RNAi-mediated management of the citrus root weevil (Diaprepes abbreviatus).

BACKGROUND: The citrus root weevil, Diaprepes abbreviatus, is a destructive agricultural pest for which molecular control options remain limited due to historically sparse genomic resources. Leveraging a comprehensive de novo transcriptome, we investigated developmental gene regulation across larval, pupal, and adult stages and identified essential targets for RNA interference (RNAi)-based intervention. RESULTS: Stage-resolved transcriptomic analyses revealed extensive transcriptional reprogramming associated with metabolism, detoxification, cuticle biosynthesis, endocrine signaling, and sensory perception. Among these, chitin synthase (DaCHS) emerged as a critical developmental gene, exhibiting pronounced up-regulation during late larval and pupal stages corresponding to intensive cuticle synthesis. Phylogenetic and structural analyses demonstrated that DaCHS is highly conserved among insects and retains canonical catalytic domains and transmembrane topology. Alpha Fold-based structural modeling and molecular docking confirmed stable interaction of DaCHS with its substrate, N-acetylglucosamine, supporting functional conservation of enzymatic activity. Oral delivery of DaCHS double-stranded RNA induced robust transcript suppression, leading to significant mortality and severe developmental defects, including larval and pupal abnormalities, and adults with disrupted wing and abdominal morphogenesis. CONCLUSION: These findings establish DaCHS as an indispensable gene for D. abbreviates development and validate transcriptome-guided RNAi as a powerful framework for target discovery. This work provides a strong molecular foundation for developing RNAi-based strategies that can be integrated into sustainable management programs for citrus root weevil control. © 2026 Society of Chemical Industry.

Animals↗

PubMed2026

Systematic identification of germ granule proteins reveals specialized roles in RNAi and small RNA inheritance.

Biomolecular condensates, such as germ granules, organize RNAi pathways critical for fertility and genome regulation. However, the protein composition and functional contributions of these condensates remain poorly defined. Here, we applied TurboID proximity labeling to the Caenorhabditis elegans germ granule protein SIMR-1, integrating mass spectrometry with genetic screening, CRISPR-based tagging, and small RNA sequencing. This systematic approach identified several previously uncharacterized germ granule proteins that contribute to fertility, germline immortality, exogenous RNAi, and transgenerational inheritance. Small RNA sequencing of 21 mutants revealed broad and class-specific defects in siRNA and miRNA biogenesis, with distinct factors associated with defects in WAGO-class 22G-RNAs, CSR-class 22G-RNAs, or histone-directed small RNAs. Among these, we identified PINT-1, a highly disordered protein that directly interacts with and is recruited to germ granules by the PIWI Argonaute PRG-1. PINT-1 is required for piRNA-dependent and -independent secondary siRNA biogenesis and germline development. Comparative genomics revealed that PINT-1 has coevolved with PRG-1 across clade V nematodes, with a conserved structured N terminus and a rapidly diverging repeat-rich intrinsically disordered region. Together, our findings expand the germ granule proteome and reveal how distinct condensate components contribute to specialized functions within the small RNA pathways, while highlighting an evolutionarily coadapted PIWI interactor critical for siRNA biogenesis.

Animals↗

PubMed2026

A robust biotechnology induces artificial genomic duplication via transient RNAi-mediated suppression of OSD1 in rice.

Ploidy manipulation is a crucial strategy for generating germplasm in crop breeding. However, artificial genomic duplication, often induced by colchicine treatment, is associated with toxicity and unpredictability. Although mutations in OSD1 have shown promise for inducing genomic duplication, the instability of ploidy across generations limits their practical application. In this study, we developed a Plant Polyploidization via Gene Interference (PPGI) system that utilizes transient RNAi-mediated suppression of OSD1 to efficiently induce artificial genomic duplication, demonstrating obvious potential for producing autotetraploids. We first validated this system by successfully generating PPGI-induced autotetraploid plants from the Taichung65 cultivar. These PPGI-induced plants exhibited notable differences from Taichung65 but resembled the existing Taichung65-4x line obtained through colchicine treatment. Haplotype analysis indicated that the OSD1 RNAi fragment is conserved across 2,908 rice cultivars. Consequently, we employed the same PPGI vector to develop autotetraploid lines from various germplasms, including another japonica cultivar, seven indica cultivars, and one Oryza rufipogon line. The probability of genomic duplication achieved by our PPGI method was higher than that obtained by colchicine treatment. Typically, autotetraploid lines exhibit severe sterility in the first generation following polyploidization. Leveraging fertile neo-tetraploid rice and the PPGI system, we designed and verified two strategies to directly induce fertile autotetraploid germplasms in the first generation, thereby substantially shortening the breeding cycle. Our method provides a universal, efficient, and non-toxic approach for inducing autotetraploid rice germplasms and contributes to enriching fertile autotetraploid rice germplasm resources.

OSD1↗

PubMed2025

RNAi screening of uncharacterized genes identifies promising druggable targets in Schistosoma japonicum.

Schistosomiasis affects more than 250 million people worldwide and is one of the neglected tropical diseases. Currently, the treatment of schistosomiasis relies on a single drug-praziquantel-which has led to increasing pressure from drug resistance. Therefore, there is an urgent need to find new treatments. The development of genome sequencing has provided valuable information for understanding the biology of schistosomes. In the genome of Schistosoma japonicum, approximately 11% of the protein-coding sequences are uncharacterized genes (UGs) annotated as "hypothetical protein" or "protein of unknown function." These poorly understood genes have been unjustifiably neglected, although some may be essential for the survival of the parasites and serve as potential drug targets. In this study, we systematically mined the highly expressed UGs in both genders of this parasite throughout key developmental stages in their mammalian host, using our previously published S. japonicum genome and RNA-seq data. By employing in vitro RNA interference (RNAi), we screened 126 UGs that lack homologs in Homo sapiens and identified 8 that are essential for the parasite vitality. We further investigated two UGs, Sjc_0002003 and Sjc_0009272, which resulted in the most severe phenotypes. Fluorescence in situ hybridization demonstrated that both genes were expressed throughout the body without sex bias. Silencing either Sjc_0002003 or Sjc_0009272 reduced the cell proliferation in the body. Furthermore, in vivo RNAi indicated both genes are required for the growth and survival of the parasites in the mammalian host. For Sjc_0002003, we further characterize the underlying molecular cause of the observed phenotype. Through RNA-seq analysis and functional studies, we revealed that silencing Sjc_0002003 reduces the expression of a series of intestinal genes, including Sjc_0007312 (hypothetical protein), Sjc_0008276 (vha-17), Sjc_0002942 (PLA2G15), and Sjc_0003646 (SJCHGC09134 protein), leading to gut dilation. Our work highlights the importance of UGs in schistosomes as promising targets for drug development in the treatment of the schistosomiasis.

Schistosoma japonicum↗

PubMed2026

IRES-like element-mediated translation of vsp1S4(-) suppresses BmCPV replication via RNAi antagonism.

Double-stranded RNA (dsRNA) viruses are thought to express proteins exclusively from their sense strand, while the antisense strand serves primarily as a replication template. Whether the antisense strand harbors hidden coding potential remains largely unexplored. Here, by integrating ribosome profiling and mass spectrometry, we identify a conserved 78-amino acid microprotein, vsp1S4(-), encoded by an antisense small open reading frame (sORFs) of the Bombyx mori cypovirus (BmCPV) genome. We demonstrate that vsp1S4(-) translation is driven by a previously unrecognized IRES-like element. Functional characterizations reveal that vsp1S4(-) localizes to the plasma membrane and acts as a negative regulator of viral replication. Mechanistically, vsp1S4(-) interacts directly with the viral RNAi suppressor NSP8, competitively disrupting the NSP8-AGO2 complex. This action restores the host's antiviral RNAi response, thereby limiting viral proliferation. Our findings challenge the conventional view of dsRNA virus coding capacity, unveil a novel viral immune evasion and replication control mechanism, and highlight antisense-encoded microproteins as potential targets for antiviral therapy.

Animals↗

PubMed2026

Transcriptomic and RNAi analyses reveal chloride channel 3-associated osmoregulation in Litopenaeus vannamei under low-salinity stress.

Chloride channels and transporters are important for cellular volume regulation and salinity adaptation in euryhaline crustaceans, yet the intestinal transcriptional relationship between plasma-membrane and intracellular chloride pathways remains unclear in Litopenaeus vannamei. In this study, RNA interference of anoctamin 1 (ANO1) was combined with intestinal transcriptome sequencing under the production-relevant low-salinity condition of salinity 3. ANO1 silencing produced a focused transcriptional response, with 16 differentially expressed genes (DEGs) identified (11 upregulated and 5 downregulated). Functional enrichment indicated that these genes were associated with transporter activity, cytoskeletal organization, extracellular matrix-receptor interaction, membrane lipid metabolism, and vesicular processes. Notably, a transcript encoding chloride channel protein 3 (CLC-3) was significantly upregulated following ANO1 knockdown, suggesting a potential transcriptional relationship between ANO1 and CLC-3 in chloride homeostasis. Based on this finding, CLC-3 was selected for full-length cDNA cloning, sequence characterization, salinity-gradient expression analysis, and RNAi-based functional assessment. The cloned CLC-3 cDNA was 2883 bp in length and encoded an 850 amino acid protein containing a conserved voltage-gated chloride channel (Voltage-CLC) domain and two cystathionine β-synthase domains. Phylogenetic analysis placed LvCLC-3 within the intracellular CLC-c clade, and tissue distribution analysis showed the highest CLC-3 expression in the intestine. Intestinal CLC-3 expression responded nonlinearly to salinity variation, peaking at salinity 20. Under salinity 3, CLC-3 knockdown reduced ANO1, Na+/K+-ATPase alpha subunit, and Na+-K+-2Cl- cotransporter transcript levels, whereas glutamate-gated chloride channel expression increased. Mild hepatopancreatic structural alterations were also observed after CLC-3 knockdown. These findings suggest that CLC-3 is a salinity-responsive intracellular chloride-transporter candidate associated with intestinal ion-transport-related transcriptional responses after ANO1 suppression in L. vannamei, although the underlying physiological mechanism requires further validation.

Animals↗

PubMed2026

Integrated RNA-seq and RNAi analyses reveal that ABCF2 is involved in defense against Vibrio parahaemolyticus in Penaeus vannamei.

The sustainable development of shrimp aquaculture is significantly compromised by Vibrio parahaemolyticus infections. Identifying host resistance genes and characterizing their immunological roles are essential for developing effective disease control strategies. In this study, we conducted a comparative transcriptomic analysis of intestinal tissues from Penaeus vannamei exhibiting varying degrees of pathological damage post-V. parahaemolyticus challenge to identify key resistance genes. KEGG enrichment analysis revealed that the ABC transporter pathway was markedly enriched among upregulated genes in both the 9 h vs 0 h and 48 h vs 0 h comparison groups. Based on the expression profiles and domain characteristics of genes within this pathway, the full transporter PvABCA3, half transporter PvABCC1, and soluble protein PvABCF2 were selected for RNAi assays. The result indicated that silencing PvABCF2, but not PvABCA3 and PvABCC1, significantly increased mortality, tissue damage, and Vibrio load in V. parahaemolyticus-challenged shrimp. Further investigation revealed that PvABCF2 silencing substantially suppressed the expression of antimicrobial peptides (AMPs), components of the proPO-activating system, and key genes involved in the JAK-STAT and NF-κB signaling pathways. These findings suggested that the increased susceptibility of shrimp to V. parahaemolyticus following PvABCF2 silencing may be associated with downregulation of these specific immune-related genes. Moreover, one SNP within PvABCF2 was found to be markedly associated with resistance to V. parahaemolyticus via SNP association analysis. Collectively, these results suggested that PvABCF2 was involved in defense response against V. parahaemolyticus and identified a potential molecular marker for disease-resistant breeding.

Animals↗

PubMed2024

Combination of computational techniques and RNAi reveal targets in Anopheles gambiae for malaria vector control.

Increasing reports of insecticide resistance continue to hamper the gains of vector control strategies in curbing malaria transmission. This makes identifying new insecticide targets or alternative vector control strategies necessary. CLassifier of Essentiality AcRoss EukaRyote (CLEARER), a leave-one-organism-out cross-validation machine learning classifier for essential genes, was used to predict essential genes in Anopheles gambiae and selected predicted genes experimentally validated. The CLEARER algorithm was trained on six model organisms: Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and employed to identify essential genes in An. gambiae. Of the 10,426 genes in An. gambiae, 1,946 genes (18.7%) were predicted to be Cellular Essential Genes (CEGs), 1716 (16.5%) to be Organism Essential Genes (OEGs), and 852 genes (8.2%) to be essential as both OEGs and CEGs. RNA interference (RNAi) was used to validate the top three highly expressed non-ribosomal predictions as probable vector control targets, by determining the effect of these genes on the survival of An. gambiae G3 mosquitoes. In addition, the effect of knockdown of arginase (AGAP008783) on Plasmodium berghei infection in mosquitoes was evaluated, an enzyme we computationally inferred earlier to be essential based on chokepoint analysis. Arginase and the top three genes, AGAP007406 (Elongation factor 1-alpha, Elf1), AGAP002076 (Heat shock 70kDa protein 1/8, HSP), AGAP009441 (Elongation factor 2, Elf2), had knockdown efficiencies of 91%, 75%, 63%, and 61%, respectively. While knockdown of HSP or Elf2 significantly reduced longevity of the mosquitoes (p<0.0001) compared to control groups, Elf1 or arginase knockdown had no effect on survival. However, arginase knockdown significantly reduced P. berghei oocytes counts in the midgut of mosquitoes when compared to LacZ-injected controls. The study reveals HSP and Elf2 as important contributors to mosquito survival and arginase as important for parasite development, hence placing them as possible targets for vector control.

Animals↗

PubMed2017

Future of rAAV Gene Therapy: Platform for RNAi, Gene Editing, and Beyond.

The use of recombinant adeno-associated viruses (rAAVs) ushered in a new millennium of gene transfer for therapeutic treatment of a number of conditions, including congenital blindness, hemophilia, and spinal muscular atrophy. rAAV vectors have remarkable staying power from a therapeutic standpoint, withstanding several ebbs and flows. As new technologies such as clustered regularly interspaced short palindromic repeat genome editing emerge, it is now the delivery tool-the AAV vector-that is the stalwart. The long-standing safety of this vector in a multitude of clinical settings makes rAAV a selling point in the advancement of approaches for gene replacement, gene knockdown, gene editing, and genome modification/engineering. The research community is building on these advances to develop more tailored delivery approaches and to tweak the genome in new and unique ways. Intertwining these approaches with newly engineered rAAV vectors is greatly expanding the available tools to manipulate gene expression with a therapeutic intent.

Dependovirus↗

PubMed2026

Genome-Wide In Vivo RNAi Screening Identifies HOXD4 as a Tumor Metastasis Suppressor in Colorectal Cancer.

Metastasis remains a major therapeutic challenge in colorectal cancer, highlighting an urgent need to elucidate its underlying molecular mechanisms. In this study, an in vivo screening system integrating genome-wide short hairpin RNA library and next-generation sequencing identifies six candidate metastasis suppressors, among which Homeobox D4 (HOXD4) shows the most pronounced effects. Clinicopathological analyses reveal significant HOXD4 downregulation in tumor tissues relative to adjacent normal tissues, with reduced expression strongly correlating with aggressive tumor features. Functional assays demonstrate that HOXD4 depletion enhances migration, invasion, and tumorsphere formation in HCT116 cells, while ectopic HOXD4 overexpression reverses these malignant phenotypes in SW620 cells. Mechanistically, HOXD4 suppresses epithelial-mesenchymal transition (EMT) by directly binding to the promoter of Forkhead box Q1 (FOXQ1), a key driver of EMT and stemness, and thereby transcriptionally repressing its expression. Immunohistochemistry confirms an inverse correlation between HOXD4 and FOXQ1 expression in clinical specimens. Rescue experiments substantiate that HOXD4 exerts its metastasis-suppressing functions via FOXQ1 regulation. Collectively, these findings not only establish an efficient platform for screening tumor metastasis suppressors, but also identify HOXD4 as a master transcriptional regulator of the FOXQ1-EMT axis, providing a promising target for metastasis interception.

Humans↗

PubMed2026

A small viral protein suppresses immune amplification by two distinct mechanisms.

Diverse viral suppressors of RNA interference (RNAi) and RNA silencing (VSRs) interact directly with core protein and/or RNA components of the host RNAi pathway. However, the specific counter-defense function of any VSR biochemical activity is fully validated only when it is shown as essential for viral infection in the wild-type but not mutant hosts defective in antiviral RNAi. Here, we investigated the role of VSR activities for direct binding to small-interfering RNA duplexes (siRNA), long double-stranded RNA (dsRNA), or RNA-dependent RNA polymerase 1 (RDR1) during plant infection by wild-type and mutant cucumber mosaic virus (CMV), a positive-strand RNA virus expressing the 110-residue 2b protein as its VSR. We demonstrate that a C-terminally truncated 2b mutant (2b1-93) active in direct binding to siRNA and dsRNA, but not RDR1, was able to suppress the amplification of virus-derived siRNAs (vsiRNA) and antiviral RNAi mediated by RDR6, but not RDR1. By contrast, an N-terminally truncated 2b mutant (2b18-110) inactive in direct binding to siRNA or dsRNA was able to suppress vsiRNA amplification and antiviral RNAi mediated by RDR1, but not RDR6, and was less effective to promote systemic CMV infection and disease development than 2b1-93. Together, our results show that whereas RDR1 suppression requires direct binding of VSR-2b to RDR1, but not siRNA or dsRNA, RDR6 suppression depends on direct binding to siRNA and dsRNA, but not RDR1. Therefore, CMV, through its VSR-2b, suppresses two parallel vsiRNA amplification pathways by distinct molecular mechanisms, and this unique property may account for the unusually wide host range of CMV.IMPORTANCEHost amplification of antiviral immunity is essential for robust control of viral infections. However, little is known about the mechanisms that viruses have evolved to suppress immune amplification in plants. Here, we characterized whole plant infection by cucumber mosaic virus (CMV) with its viral suppressor of RNA interference (RNAi) mutated to become inactive in direct binding to small-interfering RNA duplexes (siRNA), long double-stranded RNA (dsRNA), or RNA-dependent RNA polymerase 1 (RDR1). We demonstrate maximal suppression of both RDR1- and RDR6-mediated antiviral RNAi amplification by the CMV 2b protein, a viral suppressor of RNAi (VSR). Notably, whereas RDR1 suppression requires direct binding of 2b to RDR1 but not siRNA or dsRNA, RDR6 suppression depends on direct binding to siRNA and dsRNA, but not RDR1. Our findings reveal a novel counter-defense strategy evolved by a wide host range positive-strand RNA virus to suppress two pathways of immune amplification by distinct mechanisms.

Cucumovirus↗

PubMed2025

Microbe-induced gene silencing of fungal gene confers efficient resistance against Fusarium graminearum in maize.

UNLABELLED: Small RNAs (sRNAs), the main effectors of RNA interference (or RNA silencing, RNAi), mediate cell-autonomous and non-cell-autonomous gene silencing. The discoveries of trans-kingdom RNAi and interspecies RNAi have accelerated the development of RNAi-based crop protection technologies. Recently, based on interspecies RNAi, a practical technology termed microbe-induced gene silencing (MIGS) without the need of host genetic modification is developed for crop protection against Verticillium dahliae and Fusarium oxysporum in cotton and rice plants. In this study, we utilized MIGS technology to protect maize against Fusarium graminearum, which is responsible for maize stalk rot. An RNAi-engineered Trichoderma harzianum strain, Th-FgPmt2i, was exploited to generate double-stranded RNAs (dsRNAs) to trigger the silencing of the FgPTM2 gene. Our data verify that sRNAs generated from Th-FgPmt2i can silence the FgPMT2 gene via translational inhibition in F. graminearum. We further demonstrated that Th-FgPmt2i has a stronger capacity than does the T. harzianum chassis for protection of maize against F. graminearum. Coupled with our studies on crop protection against V. dahliae and F. oxysporum, our findings reveal that MIGS can be exploited to protect various crops against distinct fungal pathogens and has extensive applicability. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42994-025-00212-9.

Fusarium graminearum↗