Alternative splicing of VRF1 acts as a molecular switch to regulate stress-induced early flowering.

Plants frequently evade extreme environmental stress by initiating early flowering, yet the underlying mechanisms remain incompletely understood. Here, through extensive mutant screening, we identify a vegetative growth to reproductive growth transition factor (vrf1) mutant, which exhibits a deficiency in drought escape. Alternative splicing of VRF1 generates four isoforms, of which two encode functional proteins, VRF1-AS1 and VRF1-AS3. The proportions of VRF1-AS1 and VRF1-AS3 are modulated by environmental factors, serving as a molecular switch mediating the transition from tolerance to early flowering, irrespective of their absolute abundance. VRF1-AS1 and VRF1-AS3 competitively bind to MKK1, resulting in MKK1 phosphorylation at different sites, which opens two distinct regulatory pathways. The role of VRF1 is conserved across various conditions, and 66 Arabidopsis ecotypes suggest its central function in stress avoidance through premature flowering. In summary, our findings show that plants respond precisely and effectively to dynamic environmental changes by modulating their isoform ratios.

Sesquiterpenoids in Agarwood: Biosynthesis, Microbial Induction, and Pharmacological Activities.

Agarwood, derived from the Aquilaria genus, is widely utilized in perfumery, traditional medicine, and cultural practices throughout Asia. Agarwood is rich in terpenes, especially sesquiterpenes, which are considered to be the source of its rare and exquisite fragrance. This Review consolidates recent research on sesquiterpene biosynthesis in agarwood and the influence of fungi on these processes, alongside a discussion of the potential medicinal value of agarwood sesquiterpenes. This Review commences by elucidating the general biosynthesis of sesquiterpenes and identifying the main enzymes and transcription factors involved in the production of agarwood sesquiterpenes. This Review also summarizes the fungi associated with agarwood and highlights how commensal fungi stimulate agarwood and sesquiterpene production. We then scrutinize the pharmacological properties of sesquiterpenes, underscoring their anti-inflammatory and antimicrobial effects, which are closely linked to cellular signaling pathways, such as the NF-κB and MAPK pathways. Additionally, we review the potential therapeutic benefits of agarwood essential oil for its antidepressant properties, which are linked to the regulation of stress-related neurochemical and hormonal pathways. This Review also addresses the challenges of sustainable agarwood production, highlighting issues such as overharvesting and habitat loss while discussing the potential strategy of harnessing microbes in agarwood production to support the ecological preservation of wild resources. By advancing our knowledge of agarwood and sesquiterpene characteristics, we propose potential directions for the future application and sustainable development of agarwood research.

Deciphering the roles of bacterial and fungal communities in the formation and quality of agarwood.

Aquilaria sinensis is a significant resin-producing plant worldwide that is crucial for agarwood production. Agarwood has different qualities depending on the method with which it is formed, and the microbial community structures that are present during these methods are also diverse. Furthermore, the microbial communities of plants play crucial roles in determining their health and productivity. While previous studies have investigated the impact of microorganisms on agarwood formation, they lack comprehensiveness, particularly regarding the properties of the microbial community throughout the entire process from seedling to adult to incense formation. We collected roots, stems, leaves, flowers, fruits and other tissues from seedlings, healthy plants and agarwood-producing plants to address this gap and assess the dominant bacterial species in the microbial community structures of A. sinensis at different growth stages and their impacts on growth and agarwood formation. The bacteria and fungi in these tissues were classified and counted from different perspectives. The samples were sequenced using the Illumina sequencing platform, and sequence analyses and species annotations were performed using a range of bioinformatics tools to assess the plant community compositions. An additional comparison of the samples was conducted using diversity analyses to assess their differences. This research revealed that Listeria, Kurtzmanomyces, Ascotaiwania, Acinetobacter, Sphingobium, Fonsecaea, Acrocalymma, Allorhizobium, Bacillus, Pseudomonas, Peethambara, and Debaryomyces are potentially associated with the formation of agarwood. Overall, the data provided in this article help us understand the important roles played by bacteria and fungi in the growth and agarwood formation process of A. sinensis, will support the theoretical basis for the large-scale cultivation of A. sinensis, and provide a basis for further research on microbial community applications in agarwood production and beyond.

Unraveling the secrets: Evolution of resistance mediated by membrane proteins.

Membrane protein-mediated resistance is a multidisciplinary challenge that spans fields such as medicine, agriculture, and environmental science. Understanding its complexity and devising innovative strategies are crucial for treating diseases like cancer and managing resistant pests in agriculture. This paper explores the dual nature of resistance mechanisms across different organisms: On one hand, animals, bacteria, fungi, plants, and insects exhibit convergent evolution, leading to the development of similar resistance mechanisms. On the other hand, influenced by diverse environmental pressures and structural differences among organisms, they also demonstrate divergent resistance characteristics. Membrane protein-mediated resistance mechanisms are prevalent across animals, bacteria, fungi, plants, and insects, reflecting their shared survival strategies evolved through convergent evolution to address similar survival challenges. However, variations in ecological environments and biological characteristics result in differing responses to resistance. Therefore, examining these differences not only enhances our understanding of adaptive resistance mechanisms but also provides crucial theoretical support and insights for addressing drug resistance and advancing pharmaceutical development.

Stabilization of dimeric PYR/PYL/RCAR family members relieves abscisic acid-induced inhibition of seed germination.

Abscisic acid (ABA) is the primary preventing factor of seed germination, which is crucial to plant survival and propagation. ABA-induced seed germination inhibition is mainly mediated by the dimeric PYR/PYL/RCAR (PYLs) family members. However, little is known about the relevance between dimeric stability of PYLs and seed germination. Here, we reveal that stabilization of PYL dimer can relieve ABA-induced inhibition of seed germination using chemical genetic approaches. Di-nitrobensulfamide (DBSA), a computationally designed chemical probe, yields around ten-fold improvement in receptor affinity relative to ABA. DBSA reverses ABA-induced inhibition of seed germination mainly through dimeric receptors and recovers the expression of ABA-responsive genes. DBSA maintains PYR1 in dimeric state during protein oligomeric state experiment. X-ray crystallography shows that DBSA targets a pocket in PYL dimer interface and may stabilize PYL dimer by forming hydrogen networks. Our results illustrate the potential of PYL dimer stabilization in preventing ABA-induced seed germination inhibition.

Research Progress of Biosensor Based on Organic Photoelectrochemical Transistor.

In order to solve the food safety problem better, it is very important to develop a rapid and sensitive technology for detecting food contamination residues. Organic photoelectrochemical transistor (OPECT) biosensor rely on the photovoltage generated by a semiconductor upon excitation by light to regulate the conductivity of the polymer channels and realize biosensor analysis under zero gate bias. This technology integrates the excellent characteristics of photoelectrochemical (PEC) bioanalysis and the high sensitivity and inherent amplification ability of organic electrochemical transistor (OECT). Based on this, OPECT biosensor detection has been proven to be superior to traditional biosensor detection methods. In this review, we summarize the research status of OPECT biosensor in disease markers and food residue analysis, the basic principle, classification, and biosensing mechanism of OPECT biosensor analysis are briefly introduced, and the recent applications of biosensor analysis are discussed according to the signal strategy. We mainly introduced the OPECT biosensor analysis methods applied in different fields, including the detection of disease markers and food hazard residues such as prostate-specific antigen, heart-type fatty acid binding protein, T-2 toxin detection in milk samples, fat mass and objectivity related protein, ciprofloxacin in milk. The OPECT biosensor provides considerable development potential for the construction of safety analysis and detection platforms in many fields, such as agriculture and food, and hopes to provide some reference for the future development of biosensing analysis methods with higher selectivity, faster analysis speed and higher sensitivity.

The Art of Finding the Right Drug Target: Emerging Methods and Strategies.

Drug targets are specific molecules in biological tissues and body fluids that interact with drugs. Drug target discovery is a key component of drug discovery and is essential for the development of new drugs in areas such as cancer therapy and precision medicine. Traditional in vitro or in vivo target discovery methods are time-consuming and labor-intensive, limiting the pace of drug discovery. With the development of modern discovery methods, the discovery and application of various emerging technologies have greatly improved the efficiency of drug discovery, shortened the cycle time, and reduced the cost. This review provides a comprehensive overview of various emerging drug target discovery strategies, including computer-assisted approaches, drug affinity response target stability, multiomics analysis, gene editing, and nonsense-mediated mRNA degradation, and discusses the effectiveness and limitations of the various approaches, as well as their application in real cases. Through the review of the aforementioned contents, a general overview of the development of novel drug targets and disease treatment strategies will be provided, and a theoretical basis will be provided for those who are engaged in pharmaceutical science research. SIGNIFICANCE STATEMENT: Target-based drug discovery has been the main approach to drug discovery in the pharmaceutical industry for the past three decades. Traditional drug target discovery methods based on in vivo or in vitro validation are time-consuming and costly, greatly limiting the development of new drugs. Therefore, the development and selection of new methods in the drug target discovery process is crucial.

Immunomodulation of cuproptosis and ferroptosis in liver cancer.

According to statistics, the incidence of liver cancer is increasing yearly, and effective treatment of liver cancer is imminent. For early liver cancer, resection surgery is currently the most effective treatment. However, resection does not treat the disease in advanced patients, so finding a method with a better prognosis is necessary. In recent years, ferroptosis and cuproptosis have been gradually defined, and related studies have proved that they show excellent results in the therapy of liver cancer. Cuproptosis is a new form of cell death, and the use of cuproptosis combined with ferroptosis to inhibit the production of hepatocellular carcinoma cells has good development prospects and is worthy of in-depth discussion by researchers. In this review, we summarize the research progress on cuproptosis combined with ferroptosis in treating liver cancer, analyze the value of cuproptosis and ferroptosis in the immune of liver cancer, and propose potential pathways in oncotherapy with the combination of cuproptosis and ferroptosis, which can provide background knowledge for subsequent related research.

HDAC1: An Essential and Conserved Member of the Diverse Zn2+-Dependent HDAC Family Driven by Divergent Selection Pressure.

Zn2+-dependent histone deacetylases (HDACs) are enzymes that regulate gene expression by removing acetyl groups from histone proteins. These enzymes are essential in all living systems, playing key roles in cancer treatment and as potential pesticide targets. Previous phylogenetic analyses of HDAC in certain species have been published. However, their classification and evolutionary origins across biological kingdoms remain unclear, which limits our understanding of them. In this study, we collected the HDAC sequences from 1451 organisms and performed analyses. The HDACs are found to diverge into three classes and seven subclasses under divergent selection pressure. Most subclasses show species specificity, indicating that HDACs have evolved with high plasticity and diversification to adapt to different environmental conditions in different species. In contrast, HDAC1 and HDAC3, belonging to the oldest class, are conserved and crucial in major kingdoms of life, especially HDAC1. These findings lay the groundwork for the future application of HDACs.

Alternative Splicing, An Overlooked Defense Frontier of Plants with Respect to Bacterial Infection.

Disease represents a major problem in sustainable agricultural development. Plants interact closely with various microorganisms during their development and in response to the prevailing environment. In particular, pathogenic microorganisms can cause plant diseases, affecting the fertility, yield, and longevity of plants. During the long coevolution of plants and their pathogens, plants have evolved both molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) signaling networks in order to regulate host cells in response to pathogen infestation. Additionally, in the postgenomic era, alternative splicing (AS) has become uncovered as one of the major drivers of proteome diversity, and abnormal RNA splicing is closely associated with bacterial infections. Currently, the complexity of host-bacteria interactions is a much studied area of research that has shown steady progress over the past decade. Although the development of high-throughput sequencing technologies and their application in transcriptomes have revolutionized our understanding of AS, many mechanisms related to host-bacteria interactions remain still unclear. To this end, this review summarizes the changes observed in AS during host-bacteria interactions and outlines potential therapeutics for bacterial diseases based on existing studies. In doing so, we hope to provide guidelines for plant disease management in agriculture.

Proteogenomics-based functional genome research: approaches, applications, and perspectives in plants.

Proteogenomics (PG) integrates the proteome with the genome and transcriptome to refine gene models and annotation. Coupled with single-cell (SC) assays, PG effectively distinguishes heterogeneity among cell groups. Affiliating spatial information to PG reveals the high-resolution circuitry within SC atlases. Additionally, PG can investigate dynamic changes in protein-coding genes in plants across growth and development as well as stress and external stimulation, significantly contributing to the functional genome. Here we summarize existing PG research in plants and introduce the technical features of various methods. Combining PG with other omics, such as metabolomics and peptidomics, can offer even deeper insights into gene functions. We argue that the application of PG will represent an important font of foundational knowledge for plants.

Eukaryotic splicing machinery in the plant-virus battleground.

Plant virual infections are mainly caused by plant-virus parasitism which affects ecological communities. Some viruses are highly pathogen specific that can infect only specific plants, while some can cause widespread harm, such as tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). After a virus infects the host, undergoes a series of harmful effects, including the destruction of host cell membrane receptors, changes in cell membrane components, cell fusion, and the production of neoantigens on the cell surface. Therefore, competition between the host and the virus arises. The virus starts gaining control of critical cellular functions of the host cells and ultimately affects the fate of the targeted host plants. Among these critical cellular processes, alternative splicing (AS) is an essential posttranscriptional regulation process in RNA maturation, which amplify host protein diversity and manipulates transcript abundance in response to plant pathogens. AS is widespread in nearly all human genes and critical in regulating animal-virus interactions. In particular, an animal virus can hijack the host splicing machinery to re-organize its compartments for propagation. Changes in AS are known to cause human disease, and various AS events have been reported to regulate tissue specificity, development, tumour proliferation, and multi-functionality. However, the mechanisms underlying plant-virus interactions are poorly understood. Here, we summarize the current understanding of how viruses interact with their plant hosts compared with humans, analyze currently used and putative candidate agrochemicals to treat plant-viral infections, and finally discussed the potential research hotspots in the future. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing.

Global Analysis of Dark- and Heat-Regulated Alternative Splicing in Arabidopsis.

Alternative splicing (AS) is one of the major post-transcriptional regulation mechanisms that contributes to plant responses to various environmental perturbations. Darkness and heat are two common abiotic factors affecting plant growth, yet the involvement and regulation of AS in the plant responses to these signals remain insufficiently examined. In this study, we subjected Arabidopsis seedlings to 6 h of darkness or heat stress and analyzed their transcriptome through short-read RNA sequencing. We revealed that both treatments altered the transcription and AS of a subset of genes yet with different mechanisms. Dark-regulated AS events were found enriched in photosynthesis and light signaling pathways, while heat-regulated AS events were enriched in responses to abiotic stresses but not in heat-responsive genes, which responded primarily through transcriptional regulation. The AS of splicing-related genes (SRGs) was susceptible to both treatments; while dark treatment mostly regulated the AS of these genes, heat had a strong effect on both their transcription and AS. PCR analysis showed that the AS of the Serine/Arginine-rich family gene SR30 was reversely regulated by dark and heat, and heat induced the upregulation of multiple minor SR30 isoforms with intron retention. Our results suggest that AS participates in plant responses to these two abiotic signals and reveal the regulation of splicing regulators during these processes.

SWATH-MS-based proteogenomic analysis reveals the involvement of alternative splicing in poplar upon lead stress.

Alternative splicing (AS) regulates gene expression and increases proteomic diversity for the fine tuning of stress responses in plants, but the exact mechanism through which AS functions in plant stress responses is not thoroughly understood. Here, we investigated how AS functions in poplar (Populus trichocarpa), a popular plant for bioremediation, in response to lead (Pb) stress. Using a proteogenomic analysis, we determine that Pb stress induced alterations in AS patterns that are characterized by an increased use of nonconventional splice sites and a higher abundance of Pb-responsive splicing factors (SFs) associated with Pb-responsive transcription factors. A strong Pb(II)-inducible chaperone protein, PtHSP70, that undergoes AS was further characterized. Overexpression of its two spliced isoforms, PtHSP70-AS1 and PtHSP70-AS2, in poplar and Arabidopsis significantly enhances the tolerance to Pb. Further characterization shows that both isoforms can directly bind to Pb(II), and PtHSP70-AS2 exhibits 10-fold higher binding capacities and a greater increase in expression under Pb stress, thereby reducing cellular toxicity through Pb(II) extrusion and conferring Pb tolerance. AS of PtHSP70 is found to be regulated by PtU1-70K, a Pb(II)-inducible core SF involved in 5'-splice site recognition. Because the same splicing pattern is also found in HSP70 orthologs in other plant species, AS of HSP70 may be a common regulatory mechanism to cope with Pb(II) toxicity. Overall, we have revealed a novel post-transcriptional machinery that mediates heavy metal tolerance in diverse plant species. Our findings offer new molecular targets and bioengineering strategies for phytoremediation and provide new insight for future directions in AS research.

Microbiome-mediated signal transduction within the plant holobiont.

Microorganisms colonizing the plant rhizosphere and phyllosphere play crucial roles in plant growth and health. Recent studies provide new insights into long-distance communication from plant roots to shoots in association with their commensal microbiome. In brief, these recent advances suggest that specific plant-associated microbial taxa can contribute to systemic plant responses associated with the enhancement of plant health and performance in face of a variety of biotic and abiotic stresses. However, most of the mechanisms associated with microbiome-mediated signal transduction in plants remain poorly understood. In this review, we provide an overview of long-distance signaling mechanisms within plants mediated by the commensal plant-associated microbiomes. We advocate the view of plants and microbes as a holobiont and explore key molecules and mechanisms associated with plant-microbe interactions and changes in plant physiology activated by signal transduction.

MYB30 integrates light signals with antioxidant biosynthesis to regulate plant responses during postsubmergence recovery.

Submergence is an abiotic stress that limits agricultural production world-wide. Plants sense oxygen levels during submergence and postsubmergence reoxygenation and modulate their responses. Increasing evidence suggests that completely submerged plants are often exposed to low-light stress, owing to the depth and turbidity of the surrounding water; however, how light availability affects submergence tolerance remains largely unknown. Here, we showed that Arabidopsis thaliana MYB DOMAIN PROTEIN30 (MYB30) is an important transcription factor that integrates light signaling and postsubmergence stress responses. MYB DOMAIN PROTEIN30 protein abundance decreased upon submergence and accumulated during reoxygenation. Under submergence conditions, CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1), a central regulator of light signaling, caused the ubiquitination and degradation of MYB30. In response to desubmergence, however, light-induced MYB30 interacted with MYC2, a master transcription factor involved in jasmonate signaling, and activated the expression of the VITAMIN C DEFECTIVE1 (VTC1) and GLUTATHIONE SYNTHETASE1 (GSH1) gene families to enhance antioxidant biosynthesis. Consistent with this, the myb30 knockout mutant showed increased sensitivity to submergence, which was partially rescued by overexpression of VTC1 or GSH1. Thus, our findings uncover the mechanism by which the COP1-MYB30 module integrates light signals with cellular oxidative homeostasis to coordinate plant responses to postsubmergence stress.

Multi-stress resilience in plants recovering from submergence.

Submergence limits plants' access to oxygen and light, causing massive changes in metabolism; after submergence, plants experience additional stresses, including reoxygenation, dehydration, photoinhibition and accelerated senescence. Plant responses to waterlogging and partial or complete submergence have been well studied, but our understanding of plant responses during post-submergence recovery remains limited. During post-submergence recovery, whether a plant can repair the damage caused by submergence and reoxygenation and re-activate key processes to continue to grow, determines whether the plant survives. Here, we summarize the challenges plants face when recovering from submergence, primarily focusing on studies of Arabidopsis thaliana and rice (Oryza sativa). We also highlight recent progress in elucidating the interplay among various regulatory pathways, compare post-hypoxia reoxygenation between plants and animals and provide new perspectives for future studies.

Isolation and identification of plant growth-promoting rhizobacteria from tall fescue rhizosphere and their functions under salt stress.

Soil salinity has become one of the major factors that threaten tall fescue growth and turf quality. Plants recruit diverse microorganisms in the rhizosphere to cope with salinity stress. In this study, 15 plant growth-promoting rhizobacteria (PGPR) were isolated from the salt-treated rhizosphere of tall fescue and were annotated to 10 genera, including Agrobacterium, Fictibacillus, Rhizobium, Bhargavaea, Microbacterium, Paenarthrobacter, Pseudarthrobacter, Bacillus, Halomonas, and Paracoccus. All strains could produce indole-3-acetic acid (IAA). Additionally, eight strains exhibited the ability to solubilize phosphate and potassium. Most strains could grow on the medium containing 600 mM NaCl, such as Bacillus zanthoxyli and Bacillus altitudinis. Furthermore, Bacillus zanthoxyli and Bacillus altitudinis were inoculated with tall fescue seeds and seedlings to determine their growth-promoting effect. The results showed that Bacillus altitudinis and mixed culture significantly increased the germination rate of tall fescue seeds. Bacillus zanthoxyli can significantly increase the tillers number and leaf width of seedlings under salt conditions. Through the synergistic effect of FaSOS1, FaHKT1, and FaHAK1 genes, Bacillus zanthoxyli helps to expel the excess Na+ from aboveground parts and absorb more K+ in roots to maintain ion homeostasis in tall fescue. Unexpectedly, we found that Bacillus altitudinis displayed an inapparent growth-promoting effect on seedlings under salt stress. Interestingly, the mixed culture of the two strains was also able to alleviate, to some extent, the effects of salt stress on tall fescue. This study provides a preliminary understanding of tall fescue rhizobacteria and highlights the role of Bacillus zanthoxyli in tall fescue growth and salt tolerance.

A crosstalk of circadian clock and alternative splicing under abiotic stresses in the plants.

The circadian clock is an internal time-keeping mechanism that synchronizes the physiological adaptation of an organism to its surroundings based on day and night transition in a period of 24 h, suggesting the circadian clock provides fitness by adjusting environmental constrains. The circadian clock is driven by positive and negative elements that regulate transcriptionally and post-transcriptionally. Alternative splicing (AS) is a crucial transcriptional regulator capable of generating large numbers of mRNA transcripts from limited numbers of genes, leading to proteome diversity, which is involved in circadian to deal with abiotic stresses. Over the past decade, AS and circadian control have been suggested to coordinately regulate plant performance under fluctuating environmental conditions. However, only a few reports have reported the regulatory mechanism of this complex crosstalk. Based on the emerging evidence, this review elaborates on the existing links between circadian and AS in response to abiotic stresses, suggesting an uncovered regulatory network among circadian, AS, and abiotic stresses. Therefore, the rhythmically expressed splicing factors and core clock oscillators fill the role of temporal regulators participating in improving plant growth, development, and increasing plant tolerance against abiotic stresses.