Biology subjects

Pan, W.

Publications and source records attributed to Pan, W..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Aspergillus nidulans cell wall integrity kinase, MpkA, impacts cellular phenotypes that alter mycelial-material mechanical properties

Mycelial materials are an emerging, natural material made from filamentous fungi that have the potential to replace unsustainable materials used in numerous commercial applications (e.g., packaging, textiles, construction). Efforts to change the mechanical properties of mycelial-materials have typically involved altering growth medium, processing approaches, or fungal species. Although these efforts have shown varying levels of success, all approaches have shown there is a strong correlation between phenotype (of both fungal mycelia and mycelial materials assembly) and resultant mechanical properties. We hypothesize that genetic means can be used to generate specific fungal phenotypes, leading to mycelial materials with specific mechanical properties. To begin to test this hypothesis, we used a mutant of the model filamentous fungus, Aspergillus nidulans, with a deletion of the last kinase in the cell wall integrity (CWI) signaling pathway, mpkA. We generated one set of mycelial materials from the {Delta}mpkA deletion mutant (A1404), and another from its isogenic parent (A1405; control). When subjected to tensile testing, and compared to material generated from the control, {Delta}mpkA material has similar elastic modulus, but significantly increased ultimate tensile strength, and strain at failure. When subjected to a fragmentation assay (i.e., resistance to shear-stress), the {Delta}mpkA material also had higher relative mechanical strength. To determine possible causes for this behavior, we carried out a comprehensive set of phenotype assessments focused on: three-dimensional structure, hyphal morphology, hyphal growth behaviors, and conidial development. We find, compared to the control, material generated from the {Delta}mpkA mutant manifests significantly less development, a modified cell wall composition, larger diameter hyphae, more total biomass, higher water capacity and more densely packed material, which all appear to impact the altered mechanical properties.

bioengineering↗

bioRxiv2024

Adjuvant conditioning shapes the adaptive immune response and promotes trained immunotolerance via NLRP3/IL-1

Trained immunity enhances responsiveness of the innate immune system upon restimulation. Although adjuvants are used to enhance immune responses, we showed that repeated administration of alum, termed adjuvant conditioning (AC), establishes an immunosuppressive environment that delays allogeneic graft rejection by expanding myeloid-derived suppressor cells (MDSCs). Here, we show that AC-induced MDSCs suppress antigen specific adaptive responses both in vitro and in vivo, and that the immunosuppression is abolished in the absence of NLRP3 and IL-1 signaling. Allogeneic pancreatic islets transplanted into AC-treated NLRP3-/- mice are not protected, demonstrating that AC requires NLRP3 signaling. Finally, AC also has an immunosuppressive effect on human cells. Overall, our data show that AC establishes an immunosuppressive milieu via the NLRP3/IL-1 axis, leading to trained immunosuppression, or trained tolerance. Our findings give a potent mandate to explore the possibility to target the NLRP3/IL-1 pathway as a new promising strategy to condition transplant recipients and promote allograft tolerance.

immunology↗

bioRxiv2024

The clinical antiprotozoal drug halofuginone promotes weight loss by elevating GDF15 and FGF21

Obesity is a debilitating disease with increasing worldwide prevalence. Despite its high prevalence, specific pharmacologic intervention for obesity is challenging. Here, we report that halofuginone, an FDA-approved anti-scleroderma and anti-protozoal drug, is a promising anti-obesity agent in rodent models. Halofuginone suppressed food intake, increased energy expenditure, and resulted in weight loss in preclinical diet-induced obese mouse models, while also decreasing insulin resistance and hepatic steatosis. By combining genetic and pharmacological tools with transcriptomics, we identified that halofuginone increases FGF21 and GDF15 levels via ATF4. Using knockout mice, we show these hormones are both necessary for its anti-obesity effects. Thus, our study first reports the beneficial metabolic effects of halofuginone and underscores its utility to treat obesity and its associated metabolic complications.

pharmacology and toxicology↗

bioRxiv2024

Genetic variation in the species Arabidopsis thaliana reveals the existence of natural heat resilience factors for meiosis

Heat interferes with multiple meiotic processes leading to genome instability and sterility in flowering plants, including many crops. Despite its importance for food security, the mechanisms underlying heat tolerance of meiosis are poorly understood. In this study, we analyzed different meiotic processes in the Arabidopsis (Arabidopsis thaliana) accessions Columbia (Col) and Landsberg erecta (Ler), their F1 hybrids and F2 offspring under heat stress (37{degrees}C). At 37{degrees}C, Col exhibits significantly reduced formation of double-stand breaks (DSBs) and completely abolished homolog pairing, synapsis and crossover (CO) formation. Strikingly, Ler and Ler/Col hybrids are much less affected than Col. Interestingly, only 10% [~] 20% of F2 offspring exhibit the same heat tolerance of meiotic recombination as parents, indicating that heat resilience in Ler is controlled by the interplay of several loci. Moreover, F2 offspring show defective chromosome condensation in interkinesis, and untimely sister-chromatid segregation and/or chromosome fragmentation, the levels of which exceed those in either inbreds and/or hybrids thus implying a transgressive effect on heat tolerance of meiosis. Furthermore, correlation and cytogenetic analysis suggest that homolog pairing and/or synapsis have an impact on heat tolerance of chromosome morphology and stability during post-recombination stages under heat stress. Taken together, this study reveals the existence of natural heat resilience factors for meiosis in Arabidopsis, which have the great potential to be exploited in breeding programs. Author summaryEnvironmental temperature alterations affect meiotic recombination and/or chromosome segregation thus perturbing genetic makeup and genome stability in plants. We have previously reported that CO formation is fully abolished in Arabidopsis thaliana accession Col under heat stress (36{degrees}C-38{degrees}C) due to reduced DSB formation and impaired homolog pairing. Here, we show that in Arabidopsis thaliana accession Ler under the same high temperature conditions, both DSB and CO formation occur normally, and homolog pairing is mildly impacted, which indicate a striking difference in heat tolerance of meiotic recombination from Col. Remarkably, Col/Ler hybrids display the same heat tolerance as Ler, however, only 10% [~] 20% of F2 offspring behave the same as parents. Moreover, we found higher levels of defects in chromosome morphology and integrity, and sister-chromatid segregation in F2 population than those in both inbreds and hybrids, which suggest a transgressive effect influencing heat tolerance of meiosis. Our findings reveal that heat resilience in Arabidopsis is controlled by the interplay of multiple genomic loci, holding a great potential to be exploited in crop breeding.

plant biology↗

bioRxiv2024

Phosphorylation-induced flexibility of proto-oncogenic Bcl3 regulates transcriptional activation by NF-κB p52 homodimer

B cell lymphoma 3 (Bcl3), a member of the I{kappa}B family proteins, modulates transcription by primarily associating with NF-{kappa}B p50 and p52 homodimers. Bcl3 undergoes extensive phosphorylation, though the functions of many of these modifications remain unclear. We previously described that phosphorylation at Ser33, Ser114 and Ser446 partially switches Bcl3 from acting as an I{kappa}B-like inhibitor to a transcription regulator by associating with the (p52:p52):DNA binary complex. Here, we identified another critical phosphorylation site, Ser366. Substituting at all four residues to phospho-mimetic glutamate further enhances Bcl3s transcriptional activity. Phospho-modifications retain Bcl3s ability to stably bind p52 but induces reciprocal structural changes as revealed by HDX-MS experiments; the N-terminal region stiffens, while the C-terminus becomes more flexible. The increased flexibility allowed the Bcl3:(p52p52) binary complex to better accommodate DNA. The removal of the C-terminal 28-residues transformed Bcl3 into a transcriptional activator independent of phosphorylation. Notably, most identified mutations in Bcl3 from various cancers map to its C-terminus, suggesting the functional relevance of Bcl3 C-terminal structural flexibility and enhanced interaction with (p52p52):DNA complex to transcriptional potential and disease. Overall, this study uncovers the mechanistic basis by which phosphorylation-driven structural changes convert Bcl3 from an inhibitor to a transcriptional cofactor of NF-{kappa}B, and how deregulation of its activity through altered phosphorylation or mutation can lead to cancer.

biochemistry↗

bioRxiv2024

Photoactivated SOPP3 enables APEX2-mediated proximity labeling with high spatio-temporal resolution in live cells

Protein interactome characterized via proximity labeling (PL) and proteomic analysis is important for mechanism study in biomedical research. However, exogenous H2O2 required for engineered peroxidase, like APEX2, is cytotoxic, while biotin ligases-based PL have poor temporal resolution. Here, we showed that SOPP3, an engineered photosensitizer, could trigger APEX2 mediated PL within seconds under blue light illumination, without exogenous H2O2 or cytotoxicity. We demonstrated that APEX2 plus photoactivated SOPP3 could catalyze spatially restricted biotinylation at endoplasmic reticulum-mitochondria contact sites and cell-cell interface. Through fusing APEX2 and SOPP3 as a chimeric probe, we showed that APEX2-SOPP3 also works well in multiple subcellular locations, including cell surface. Notably, either APEX2 plus SOPP3, or chimeric APEX2-SOPP3 requires 10 folds lower illumination power, compared to that for light-oxygen-voltage protein alone mediated PL, and has better response to illumination in terms of PL in time course with little cytotoxicity. Thus, this new PL technology paves an avenue to characterize molecular dynamics of key biomedical events with high spatial-temporal resolution, efficiency, and flexible applicability.

molecular biology↗

bioRxiv2024

The Effects of Locus Coeruleus Optogenetic Stimulation on Global Spatiotemporal Patterns in Rats

Whole-brain intrinsic activity as detected by resting-state fMRI can be summarized by three primary spatiotemporal patterns. These patterns have been shown to change with different brain states, especially arousal. The noradrenergic locus coeruleus (LC) is a key node in arousal circuits and has extensive projections throughout the brain, giving it neuromodulatory influence over the coordinated activity of structurally separated regions. In this study, we used optogenetic-fMRI in rats to investigate the impact of LC stimulation on the global signal and three primary spatiotemporal patterns. We report small, spatially specific changes in global signal distribution as a result of tonic LC stimulation, as well as regional changes in spatiotemporal patterns of activity at 5 Hz tonic and 15 Hz phasic stimulation. We also found that LC stimulation had little to no effect on the spatiotemporal patterns detected by complex principal component analysis. These results show that the effects of LC activity on the BOLD signal in rats may be small and regionally concentrated, as opposed to widespread and globally acting.

neuroscience↗

bioRxiv2024

A 10-valent composite mRNA vaccine against both influenza and COVID-19

The COVID-19 pandemic caused by SARS-CoV-2 viruses has had a persistent and significant impact on global public health for four years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19. Author summaryAmidst the ongoing and emerging respiratory viral threats, particularly the concurrent and sequential spread of SARS-CoV-2 and influenza, our research introduces FLUCOV-10. This novel mRNA-based combination vaccine, designed to counteract both influenza and COVID-19, by incorporating genes for surface glycoproteins from various influenza viruses and SARS-CoV-2 variants. This combination vaccine showed highly effective in preclinical trials, generating strong immune responses, and ensuring protection against both matching and heterologous strains of influenza and SARS-CoV-2. FLUCOV-10 represents a significant step forward in our ability to address respiratory viral threats, showcasing potential as a singular, adaptable vaccine solution for global health challenges.

microbiology↗

bioRxiv2024

Ultraviolet attenuates centromere-mediated meiotic genome stability and alters gametophytic ploidy consistency in flowering plants

Ultraviolet (UV) radiation influences development and genome stability in organisms; however, its impacts on meiosis, a special cell division essential for the delivery of genetic information over generations in eukaryotes, remain not yet elucidated. In this study, we demonstrate that UV attenuates the centromere-mediated meiotic chromosome stability and induces unreduced gametes in Arabidopsis thaliana. We show that UV reduces crossover (CO) rate but does not interfere with meiotic chromosome integrity. Functional centromere-specific histone 3 (CENH3) is required for the obligate CO formation, and plays a role in protection of homolog synapsis and sister-chromatid cohesion under UV stress. Moreover, UV specifically alters the orientation and organization of spindles and phragmoplasts at meiosis II, resulting in meiotic restitution and unreduced gametes. Further, we determine that UV-induced meiotic restitution does not rely on the UV Resistance Locus8-mediated UV perception and the Tapetal Development and Function1- and Aborted Microspores-dependent tapetum development, but occurs possibly via impacted JASON function and downregulated Parallel Spindle1. This study sheds light on the impacts of UV on meiotic genome stability and gametophytic ploidy consistency, which thus may influence genome evolution in flowering plants.

plant biology↗

bioRxiv2023

CentIER: accurate centromere identification for plant genomes with sequence specificity information

Centromere identification is one of the important problems in genomics, providing a foundation for the studies of centromeres in aspects of composition, functionality, evolution, inheritance, and variation. The existing wet-experiment-based method is costly and time-consuming, while the bioinformatic method can only detect tandem repeats losing non-repetitive sequence regions in the centromere. To address these shortcomings, we introduce a new pipeline, CentIER, for the automatic and accurate identification and annotation of centromere regions by taking advantage of the sequence specificity information. CentIER only requires users to input the genomic sequence, and then it can partition the centromeric region from a chromosome, identify tandem repeat monomers, annotate retrotransposons, and ultimately output visualized results. By referencing the experimentally determined centromere regions, it was discovered that the predictive accuracy of centromere recognition by CentIER exceeded 90%. Following the evaluation of CentIERs accuracy, it was applied to investigate the sequence and distribution characteristics of centromeric retrotransposons and tandem repeat sequences of different species, providing insights into these traits in monocotyledonous and dicotyledonous plants.

bioinformatics↗

bioRxiv2023

Reference-guided automatic assembly of genomic tandem repeats with only HiFi and Hi-C data enables population-level analysis

The existing de novo methods of complete genome assembly are not able to generate large-scale pangenomes with complete assemblies due to the shortcomings such as requiring multiple types of sequencing data of high price, requiring large amount of manual curation, and not being able to achieve haplotype-resolved complete assembly of long tandem repeats in most situations. To solve this problem, in this study, we propose a new genome assembly mode called reference-guided assembly which relies on the reference information to recall the reads for complex genomic regions of interest and assembles them in de novo-like way. As a proof-of-concept, we developed an algorithm TRFill which can reassemble or fill the gaps of tandem repeats in chromosome-level assembly in either haploid or diploid way using only HiFi and Hi-C data. The experimental results on human centromeres and tomato subtelomeres show that TRFill successfully improved the completeness and correctness of about two thirds of the tested tandem repeat sequences. Furthermore, TRFill improved the completeness of subtelomeric tandem repeats by 50% in a recently published tomato pangenome, enabling a population-level analysis of the subtelomeric tandem repeats, which found the local law of sequence similarity of tandem repeats providing theoretical basis for reference-guided assembly in turn.

bioinformatics↗

bioRxiv2023

Alternate splice variants of the mitochondrial fission protein DNM1L/Drp1 regulate mitochondrial dynamics and cell fate in ovarian cancer.

Aberrant mitochondrial fission/fusion dynamics have been reported in cancer cells. While post translational modifications are known regulators of the mitochondrial fission/fusion machinery, we show that alternative splice variants of the fission protein Drp1 (DNM1L) have specific and unique roles in cancer, adding to the complexity of mitochondrial fission/fusion regulation in tumor cells. Ovarian cancer specimens express an alternative splice transcript variant of Drp1 lacking exon 16 of the variable domain, and high expression of this splice variant relative to other transcripts is associated with poor patient outcome. Unlike the full-length variant, expression of Drp1 lacking exon 16 leads to decreased association of Drp1 to mitochondrial fission sites, more fused mitochondrial networks, enhanced respiration, and TCA cycle metabolites, and is associated with a more metastatic phenotype in vitro and in vivo. These pro-tumorigenic effects can also be inhibited by specific siRNA-mediated inhibition of the endogenously expressed transcript lacking exon 16. Moreover, lack of exon 16 abrogates mitochondrial fission in response to pro-apoptotic stimuli and leads to decreased sensitivity to chemotherapeutics. These data emphasize the significance of the pathophysiological consequences of Drp1 alternative splicing and divergent functions of Drp1 splice variants, and strongly warrant consideration of Drp1 splicing in future studies.

cancer biology↗

bioRxiv2023

Comprehensive Assessment of Eleven de novo HiFi Assemblers on Complex Eukaryotic Genomes and Metagenomes

BackgroundPacific Bioscience HiFi sequencing technology generates long reads (>10 kbp) with very high accuracy (less than 0.01% sequencing error). While several de novo assembly tools are available for HiFi reads, there are no comprehensive studies on the evaluation of these assemblers. ResultsWe evaluated the performance of eleven de novo HiFi assemblers on (i) real data for three eukaryotic genomes, (ii) 34 synthetic datasets with different ploidy, sequencing coverage levels, heterozygosity rates and sequencing error rates, (iii) one real metagenomic dataset, and (iv) five synthetic metagenomic datasets with different composition abundance and heterozygosity rates. The nine assemblers were evaluated using QUAST (Quality Assessment Tool) and BUSCO (Benchmarking Universal Single-Copy Ortholog). We also used several additional criteria, namely, completion rate, single-copy completion rate, duplicated completion rate, average proportion of largest category, average distance difference, quality value, run-time and memory utilization. On complex eukaryotic genomes, Hifiasm had a clear advantage over the other assemblers in all tested experiments. On synthetic datasets, Hifiasm, HiCanu, and HiFlye performed equally well. Shasta and Peregrine had good performance across varying ploidy, but required high computational resources. On metagenomic datasets, Hifiasm-meta demonstrated a clear advantage over other assemblers. ConclusionWe carried out a comprehensive benchmarking study of commonly used assemblers on complex eukaryotic genomes and metagenomes. Our study will help the research community to choose the most appropriate assembler for their data and identify possible improvements in assembly algorithms.

genomics↗

bioRxiv2023

Genetic basis of expression and splicing underlying spike architecture in wheat (Triticum aestivum L.)

IntroductionWheat is one of the most important staple crops worldwide, and an important source of human protein and mineral element intake. Continuously increasing stable production of wheat is critical for global food security under the challenge of population growth and limited resource input. ObjectiveSpike architecture determines the potential grain yield of wheat. However, the mechanisms of transcriptional regulation of spike architecture in wheat remain largely unknown, limiting further genetic improvement of wheat yield. In this study we explored the genetic basis of spike architecture in wheat. MethodsPopulation RNA-seq methods were used to identify the eQTLs and sQTLs associated with spike architecture and applied this to dissection of the genetic basis of gene expression and splicing controlling these complex yield-related traits. ResultsIn total, 4,143 expression quantitative trait loci (eQTLs) and 12,933 splice QTLs (sQTLs) were identified in wheat based on 178 RNA-seq samples, revealing 774 cis-eQTLs and 321 cis-sQTLs for 86 eGenes and 73 sGenes, respectively. Integration of eQTLs and sQTLs with genome-wide association study (GWAS) identified dozens of additional novel candidate genes that may contribute to spike-related traits. Gene network analysis showed that eQTLs and sQTLs were widely involved in the co-expression modules that regulate wheat spike architecture. Notably, the eQTL locus AX-108754757 regulated the expression of 5 eGenes that negatively controled grain number per spike. AX-111592099 regulated both the splicing and expression of TraesCS7B02G442100, encoding an E3 ubiquitin ligase, and playing a central role in regulating spike length. ConclusionThis study provides new insights into the genetic basis of spike architecture. This improved understanding of spike-related traits in wheat will contribute to more rapid genetic improvement.

plant biology↗

bioRxiv2023

A bootstrap model comparison test for identifying genes with context-specific patterns of genetic regulation

Understanding how genetic variation affects gene expression is essential for a complete picture of the functional pathways that give rise to complex traits. Although numerous studies have established that many genes are differentially expressed in distinct human tissues and cell types, no tools exist for identifying the genes whose expression is differentially regulated. Here we introduce DRAB (Differential Regulation Analysis by Bootstrapping), a gene-based method for testing whether patterns of genetic regulation are significantly different between tissues or other biological contexts. DRAB first leverages the elastic net to learn context-specific models of local genetic regulation and then applies a novel bootstrap-based model comparison test to check their equivalency. Unlike previous model comparison tests, our proposed approach can determine whether population-level models have equal predictive performance by accounting for the variability of feature selection and model training. We validated DRAB on mRNA expression data from a variety of human tissues in the Genotype-Tissue Expression (GTEx) Project. DRAB yielded biologically reasonable results and had sufficient power to detect genes with tissue-specific regulatory profiles while effectively controlling false positives. By providing a framework that facilitates the prioritization of differentially regulated genes, our study enables future discoveries on the genetic architecture of molecular phenotypes.

bioinformatics↗

bioRxiv2023

Inferring a directed acyclic graph of phenotypes from GWAS summary statistics

SO_SCPLOWUMMARYC_SCPLOWEstimating phenotype networks is a growing field in computational biology. It deepens the understanding of disease etiology and is useful in many applications. In this study, we present a method that constructs a phenotype network by assuming a Gaussian linear structure model embedding a directed acyclic graph (DAG). We utilize genetic variants as instrumental variables and show how our method only requires access to summary statistics from a genome-wide association study (GWAS) and a reference panel of genotype data. Besides estimation, a distinct feature of the method is its summary statistics-based likelihood ratio test on directed edges. We applied our method to estimate a causal network of 29 cardiovascular-related proteins and linked the estimated network to Alzheimers disease (AD). A simulation study was conducted to demonstrate the effectiveness of this method. An R package sumdag implementing the proposed method, all relevant code, and a Shiny application are available at https://github.com/chunlinli/sumdag.

molecular biology↗

bioRxiv2023

Real-Time Quantification of Cell Mechanics and Functions by Double Resonator Piezoelectric Cytometry -Theory and Study of Cellular Adhesion of HUVECs

Cell mechanics is closely associated with cellular structure and function. However, the inability to measure both cellular force and viscoelasticity of statistically significant number of cells noninvasively remains a challenge for quantitative characterizations of various cellular functions and practical applications. Here a double resonator piezoelectric cytometry (DRPC), using AT and BT cut quartz crystals of the same frequency and surface morphology is developed to simultaneously quantify the cells-generated forces ({Delta}S) and viscoelastic moduli (G', G'') of a population of isolated single cells or cells with different degrees of cell-cell interactions in a non-invasive and real time manner. DRPC captures the dynamic mechanical parameters {Delta}S and G', G'' during the adhesions of human umbilical vein endothelial cells (HUVECs) under different ligand densities of adhesion molecules fibronectin or Arg-Gly-Asp (RGD) modified on the gold surfaces of 9 MHz AT and BT cut quartz crystals, and different seeding densities of HUVECs. It is found that both the ligand density and cell seeding density affect the magnitudes of {Delta}S and G', G'' and their correlations are revealed for the first time by DRPC. The validity of DRPC is further verified by mechanical changes of the cells in response to treatments with cytoskeleton regulators.

biophysics↗

bioRxiv2022

A pair of NLRs coordinately modulates NRC3-mediated ETI responses to facilitate age-dependent immunity

Two NLRs (Nucleotide-binding and Leucine-rich repeat Receptors) adjacent to each other on a locus, termed as paired NLRs, may act separately for effector recognition and subsequent signaling activation to mediate effector-triggered immunity (ETI) in many plants. However, it is largely unknown about their distribution and functions in Solanaceae species, in which NLR-Hs (Helpers NLR REQUIRED FOR CELL DEATHs) have been extensively studied. Here, we identified paired NLRs in Solanaceae species and found they harbor paired NLRs ranging from 6 to 100, which are significantly negatively correlated with the numbers of NLR-Hs. N. benthamiana has six paired NLRs, among which silencing of NRCX exhibits phenotypes of dwarfism and accelerated senescence. Importantly, NRCX-silencing phenotypes could be restored by simultaneously silencing its head-to-head NLR pair, thus we named it as NRCY. NRCX/Y pair is specific in Solanaceae species. NRCY contains non-canonical walker B and MHD motifs, but could not induce autoactive cell death in N. benthamiana. Instead of that, silencing NRCY impaired cell death triggered by Sw5b-Nsm and NRC3D480V, indicating NRCY is also an NLR modulator like NRCX. Furthermore, NRCX suppression of Sw5b-Nsm and NRC3-mediated cell death is dependent on NRCY. Remarkably, we found that NRCX and NRCY expressions were induced during plant senescence, while NRCY was induced more than NRCX. Accordingly, the plant resistance was stronger during maturation, indicated NRCX/Y might be involved in age-dependent resistance. Our study reveals one of the paired NLRs coordinately regulates ETI to facilitate age-dependent immunity.

plant biology↗