Search Results (13)

Plant-derived small RNAs (sRNAs) have garnered significant attention in nucleic acid therapeutics, driven by their distinctive cross-kingdom regulatory capabilities and extensive therapeutic promise. These sRNAs exhibit a wide range of pharmacological effects, including pulmonary protection, antiviral, anti-inflammatory, and antitumor activities, underscoring their substantial potential for clinical translation. A key advantage lies in their delivery, facilitated by plant-specific nanovesicular carriers—such as plant exosomes, herbal decoctosomes, and bencaosomes—which protect sRNAs from gastrointestinal degradation and enable precise, tissue-specific targeting. This review provides a comprehensive analysis of plant-derived sRNAs, detailing their classification, gene-silencing mechanisms, and nanovesicle-mediated cross-kingdom delivery strategies. It further explores their therapeutic potential and underlying molecular mechanisms in major human diseases. Additionally, we critically evaluate current technical challenges and propose future directions to advance the development of plant-derived sRNAs for precision therapeutics. This work aims to offer a robust theoretical framework and practical guidance for the clinical advancement of plant-derived sRNA-based therapies. Full article

Cross-kingdom infections, where pathogens from one kingdom infect organisms of another, were historically regarded as rare anomalies with minimal concern. However, emerging evidence reveals their increasing prevalence and potential to disrupt the delicate balance between plant, animal, and human health systems. Traditionally recognized as plant-specific, a subset of phytopathogens, including certain fungi, bacteria, viruses, and nematodes, have demonstrated the capacity to infect non-plant hosts, particularly immunocompromised individuals. These pathogens exploit conserved molecular mechanisms, such as immune evasion strategies, stress responses, and effector proteins, to breach host-specific barriers and establish infections. Specifically, fungal pathogens like Fusarium spp. and Colletotrichum spp. employ toxin-mediated cytotoxicity and cell-wall-degrading enzymes, while bacterial pathogens, such as Pseudomonas syringae, utilize type III secretion systems to manipulate host immune responses. Viral and nematode phytopathogens also exhibit molecular mimicry and host-derived RNA silencing suppressors to facilitate infections beyond plant hosts. This review features emerging cases of phytopathogen-driven animal and human infections and dissects the key molecular and ecological determinants that facilitate such cross-kingdom transmission. It also highlights critical drivers, including pathogen plasticity, horizontal gene transfer, and the convergence of environmental and anthropogenic stressors that breach traditional host boundaries. Furthermore, this review focuses on the underlying molecular mechanisms that enable host adaptation and the evolutionary pressures shaping these transitions. To address the complex threats posed by cross-kingdom phytopathogens, a comprehensive One Health approach that bridges plant, animal, and human health strategies is advocated. Integrating molecular surveillance, pathogen genomics, AI-powered predictive modeling, and global biosecurity initiatives is essential to detect, monitor, and mitigate cross-kingdom infections. This interdisciplinary approach not only enhances our preparedness for emerging zoonoses and phytopathogen spillovers but also strengthens ecological resilience and public health security in an era of increasing biological convergence. Full article

This review highlights the emerging role of cross-kingdom RNA interference in plant–microbe interactions, particularly the transfer of sRNAs from microbes to plants and vice versa, emphasizing the importance of this mechanism in both mutualistic and pathogenic contexts. As plants adapted to terrestrial life, they formed symbiotic relationships with microbes, essential for nutrient uptake and defense. Emerging evidence underscores sRNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs), as critical regulators of gene expression and immune responses in plant–microbe interactions. In mutualistic symbioses, such as mycorrhizal fungi and nitrogen-fixing bacteria associations, sRNAs are hypothesized to regulate nutrient exchange and symbiotic stability. In pathogenic scenarios, microbes utilize sRNAs to undermine plant defenses, while plants employ strategies like host-induced gene silencing (HIGS) to counteract these threats. We further explore the emerging role of extracellular vesicles (EVs) in sRNA transport, which is critical for facilitating interspecies communication in both pathogenic and mutualistic contexts. Although the potential of ckRNAi in mutualistic interactions is promising, the review highlights the need for further experimental validation to establish its true significance in these relationships. By synthesizing current research, this review highlights the intricate molecular dialogues mediated by sRNAs in plant–microbe interactions and identifies critical gaps, proposing future research directions aimed at harnessing these mechanisms for agricultural advancements. Full article

Recent advancements in the field of plant–pathogen interactions have spotlighted the role of extracellular vesicles (EVs) as pivotal mediators of cross-kingdom communication, offering new vistas for enhancing crop protection strategies. EVs are instrumental in the transport of small regulatory RNAs (sRNAs) and other bioactive molecules across species boundaries, thus playing a critical role in the molecular warfare between plants and pathogens. This review elucidates the sophisticated mechanisms by which plants utilize EVs to dispatch sRNAs that silence pathogenic genes, fortifying defenses against microbial threats. Highlighting both eukaryotic and prokaryotic systems, this review delves into the biogenesis, isolation, and functional roles of EVs, illustrating their importance not only in fundamental biological processes but also in potential therapeutic applications. Recent studies have illuminated the significant role of EVs in facilitating communication between plants and pathogens, highlighting their potential in host-defense mechanisms. However, despite these advancements, challenges remain in the efficient isolation and characterization of plant-derived EVs. Overcoming these challenges is critical for fully harnessing their potential in developing next-generation crop protection strategies. This review proposes innovative strategies for utilizing RNA-based interventions delivered via EVs to bolster plant resilience against diseases. By integrating the latest scientific findings with practical applications in agriculture, this review aims to enhance the connection between fundamental plant biology and the development of innovative crop management technologies. Full article

RNA interference (RNAi) shows great potential in plant defense against pathogens through RNA-mediated sequence-specific gene silencing. Among RNAi-based plant protection strategies, spray-induced gene silencing (SIGS) is considered a more promising approach because it utilizes the transfer of exogenous RNA between plants and microbes to silence target pathogen genes. The application of nanovesicles significantly enhances RNA stability and delivery efficiency, thereby improving the effectiveness of SIGS and further enhancing plant resistance to diseases and pathogens. This review explores the role of RNAi in plant protection, focusing on the cross-kingdom transport of small RNAs (sRNAs) via extracellular vesicles. It also explores the potential of nanotechnology to further optimize RNA-based plant protection, offering innovative tools and methods in modern plant biotechnology. Full article

Our duty to conserve global natural ecosystems is increasingly in conflict with our need to feed an expanding population. The use of conventional pesticides not only damages the environment and vulnerable biodiversity but can also still fail to prevent crop losses of 20–40% due to pests and pathogens. There is a growing call for more ecologically sustainable pathogen control measures. RNA-based biopesticides offer an eco-friendly alternative to the use of conventional fungicides for crop protection. The genetic modification (GM) of crops remains controversial in many countries, though expression of transgenes inducing pathogen-specific RNA interference (RNAi) has been proven effective against many agronomically important fungal pathogens. The topical application of pathogen-specific RNAi-inducing sprays is a more responsive, GM-free approach to conventional RNAi transgene-based crop protection. The specific targeting of essential pathogen genes, the development of RNAi-nanoparticle carrier spray formulations, and the possible structural modifications to the RNA molecules themselves are crucial to the success of this novel technology. Here, we outline the current understanding of gene silencing pathways in plants and fungi and summarize the pioneering and recent work exploring RNA-based biopesticides for crop protection against fungal pathogens, with a focus on spray-induced gene silencing (SIGS). Further, we discuss factors that could affect the success of RNA-based control strategies, including RNA uptake, stability, amplification, and movement within and between the plant host and pathogen, as well as the cost and design of RNA pesticides. Full article

It was shown that microRNAs (miRNAs) play an important role in the synthesis of milk fat; thus, this manuscript evaluated whether exogenous miRNA (xeno-miRNAs) from alfalfa could influence the milk fat content in dairy cows. At first, mtr-miR168b was screened from dairy cow milk and blood. Then, EdU staining, flow cytometry, Oil Red O staining, qRT-PCR, and WB were applied to explore the effect of xeno-miR168b on the proliferation, apoptosis, and lipid metabolism of bovine mammary epithelial cells (BMECs). Finally, in order to clarify the pathway that regulated the lipid metabolism of BMECs using xeno-miR168b, a double-luciferase reporter assay was used to verify the target gene related to milk fat. These results showed that overexpression of xeno-miR168b inhibited cell proliferation but promoted apoptosis, which also decreased the expression of several lipid metabolism genes, including PPARγ, SCD1, C/EBPβ, and SREBP1, significantly inhibited lipid droplet formation, and reduced triglyceride content in BMECs. Furthermore, the targeting relationship between CPT1A and xeno-miR168b was determined and it was confirmed that CPT1A silencing reduced the expression of lipid metabolism genes and inhibited fat accumulation in BMECs. These findings identified xeno-miR168b from alfalfa as a cross-kingdom regulatory element that could influence milk fat content in dairy cows by modulating CPT1A expression. Full article

Fungal plant pathogens use proteinaceous effectors as well as newly identified secondary metabolites (SMs) and small non-coding RNA (sRNA) effectors to manipulate the host plant’s defense system via diverse plant cell compartments, distinct organelles, and many host genes. However, most molecular studies of plant–fungal interactions have focused on secreted effector proteins without exploring the possibly equivalent functions performed by fungal (SMs) and sRNAs, which are collectively known as “non-proteinaceous effectors”. Fungal SMs have been shown to be generated throughout the plant colonization process, particularly in the early biotrophic stages of infection. The fungal repertoire of non-proteinaceous effectors has been broadened by the discovery of fungal sRNAs that specifically target plant genes involved in resistance and defense responses. Many RNAs, particularly sRNAs involved in gene silencing, have been shown to transmit bidirectionally between fungal pathogens and their hosts. However, there are no clear functional approaches to study the role of these SM and sRNA effectors. Undoubtedly, fungal SM and sRNA effectors are now a treasured land to seek. Therefore, understanding the role of fungal SM and sRNA effectors may provide insights into the infection process and identification of the interacting host genes that are targeted by these effectors. This review discusses the role of fungal SMs and sRNAs during plant-fungal interactions. It will also focus on the translocation of sRNA effectors across kingdoms, the application of cross-kingdom RNA interference in managing plant diseases and the tools that can be used to predict and study these non-proteinaceous effectors. Full article

RNA-based strategies for plant disease management offer an attractive alternative to agrochemicals that negatively impact human and ecosystem health and lead to pathogen resistance. There has been recent interest in using mycoviruses for fungal disease control after it was discovered that some cause hypovirulence in fungal pathogens, which refers to a decline in the ability of a pathogen to cause disease. Cryphonectria parasitica, the causal agent of chestnut blight, has set an ideal model of management through the release of hypovirulent strains. However, mycovirus-based management of plant diseases is still restricted by limited approaches to search for viruses causing hypovirulence and the lack of protocols allowing effective and systemic virus infection in pathogens. RNA interference (RNAi), the eukaryotic cell system that recognizes RNA sequences and specifically degrades them, represents a promising. RNA-based disease management method. The natural occurrence of cross-kingdom RNAi provides a basis for host-induced gene silencing, while the ability of most pathogens to uptake exogenous small RNAs enables the use of spray-induced gene silencing techniques. This review describes the mechanisms behind and the potential of two RNA-based strategies, mycoviruses and RNAi, for plant disease management. Successful applications are discussed, as well as the research gaps and limitations that remain to be addressed. Full article

Plants have evolved defense mechanisms to suppress viral transcription and replication by transcriptional and post-transcriptional gene silencing mediated by virus-derived small interfering RNAs (vsiRNAs). Based on this response, virus-induced gene silencing (VIGS)-based technology has been developed to silence target genes on either host plants or insect pests. This mechanism could also be used for the silencing of genes of interest in the medical field. We used the VIGS vector pEuMV-YP:Krt18, which was obtained by inserting the Mus musculus (M. musculus) Krt18 sequence into pEuMV-YP:ΔAV1. The objective was to evaluate the capacity of pEuMV-YP:Krt18 to induce Nicotiana benthamiana (N. benthamiana) production of vsiRNAs of a specific sequence that belongs to neither the plant genome nor the wild virus genome, which were used to induce cross-kingdom gene silencing between plants and mammals. The percentage of vsiRNA for each viral gene was calculated from an sRNA library of N. benthamiana plants infected by pEuMV-YP: Krt18. When the vsiRNAs were characterized, it was found that they corresponded to all the genes of the pEuMV-YP:Krt18 vector. These vsiRNAs induced the silencing of the Krt18 gene in M. musculus macrophages, supporting the ability to use VIGS vectors in plants as biofactories for the production of sRNAs that induce gene silencing in mammals. Full article

Small RNAs represent a class of small but powerful agents that regulate development and abiotic and biotic stress responses during plant adaptation to a constantly challenging environment. Previous findings have revealed the important roles of small RNAs in diverse cellular processes. The recent discovery of bidirectional trafficking of small RNAs between different kingdoms has raised many interesting questions. The subsequent demonstration of exosome-mediated small RNA export provided a possible tool for further investigating how plants use small RNAs as a weapon during the arms race between plant hosts and pathogens. This review will focus on discussing the roles of small RNAs in plant immunity in terms of three aspects: the biogenesis of extracellular small RNAs and the transportation and trafficking small RNA-mediated gene silencing in pathogens. Full article

Small RNAs (sRNAs), a class of regulatory non-coding RNAs around 20~30-nt long, including small interfering RNAs (siRNAs) and microRNAs (miRNAs), are critical regulators of gene expression. Recently, accumulating evidence indicates that sRNAs can be transferred not only within cells and tissues of individual organisms, but also across different eukaryotic species, serving as a bond connecting the animal, plant, and microbial worlds. In this review, we summarize the results from recent studies on cross-kingdom sRNA communication. We not only review the horizontal transfer of sRNAs among animals, plants and microbes, but also discuss the mechanism of RNA interference (RNAi) signal transmission via cross-kingdom sRNAs. We also compare the advantages of host-induced gene silencing (HIGS) and spray-induced gene silencing (SIGS) technology and look forward to their applicable prospects in controlling fungal diseases. Full article

Biotic stresses do damage to the growth and development of plants, and yield losses for some crops. Confronted with microbial infections, plants have evolved multiple defense mechanisms, which play important roles in the never-ending molecular arms race of plant–pathogen interactions. The complicated defense systems include pathogen-associated molecular patterns (PAMP) triggered immunity (PTI), effector triggered immunity (ETI), and the exosome-mediated cross-kingdom RNA interference (CKRI) system. Furthermore, plants have evolved a classical regulation system mediated by miRNAs to regulate these defense genes. Most of the genes/small RNAs or their regulators that involve in the defense pathways can have very rapid evolutionary rates in the longitudinal and horizontal co-evolution with pathogens. According to these internal defense mechanisms, some strategies such as molecular switch for the disease resistance genes, host-induced gene silencing (HIGS), and the new generation of RNA-based fungicides, have been developed to control multiple plant diseases. These broadly applicable new strategies by transgene or spraying ds/sRNA may lead to reduced application of pesticides and improved crop yield. Full article