Several quantitative trait genes (QTGs) related to rice heading date, a key factor for crop development and yield, have been identified, along with complex interactions among genes. However, a comprehensive genetic interaction network for these QTGs has not yet been established. In this study, we use 18K-rice lines to identify QTGs and their epistatic interactions affecting rice heading date. We identify 264 pairs of interacting QTL and construct a comprehensive genetic network of these QTL. On average, the epistatic effects of QTL pairs are estimated to be approximately 12.5% of additive effects of identified QTL. Importantly, epistasis vary among different alleles of several heading date genes. Additionally, 57 pairs of interacting QTGs are also significant in their epistatic effects on 12 other agronomic traits. The identified QTL genetic interactions are further validated using near-isogenic lines, yeast two-hybrid, and split-luciferase complementation assays. Overall, this study provides a genetic network of rice heading date genes, which plays a crucial role in regulating rice heading date and influencing multiple related agronomic traits. This network serves as a foundation for understanding the genetic mechanisms of rice quantitative traits and for advancing molecular breeding efforts.

Colitis-associated colorectal cancer (CAC), a serious complication of ulcerative colitis (UC), is associated with a poor prognosis. The vitamin D receptor (VDR) is recognized for its protective role in UC and CAC through the maintenance of intestinal barrier integrity and the regulation of inflammation. This study demonstrates a significant reduction in mA-related genes, particularly methyltransferase like 14 (METTL14), in UC and CAC patients and identifies an association between METTL14 and VDR. In the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced mouse model, vitamin D treatment increases METTL14 expression and reduces tumor burden, while Vdr-knockout mice exhibit lower METTL14 levels and increased tumorigenesis. In vitro, the VDR agonist calcipotriol upregulates METTL14 in NCM460 cells, with this effect attenuated by VDR knockdown. VDR knockdown in DLD-1 colon cancer cells decreases METTL14 expression and promotes proliferation, which is reversed by METTL14 overexpression. Mechanistic studies reveal that VDR regulates METTL14 expression via promoter binding, modulating key target genes such as SOX4, DROSH, and PHLPP2. This study highlights the role of the VDR-METTL14 axis as a protective mechanism in CAC and suggests its potential as a therapeutic target for preventing and treating CAC.

Mitochondria are semi-autonomous organelles present in eukaryotic cells, containing their own genome and transcriptional machinery. However, their functions are intricately linked to proteins encoded by the nuclear genome. Mitochondrial transcription termination factors (mTERFs) are nucleic acid-binding proteins involved in RNA splicing and transcription termination within plant mitochondria and chloroplasts. Despite their recognized importance, the specific roles of mTERF proteins in maize remain largely unexplored. Here, we clone and functionally characterize the maize mTERF18 gene. Our findings reveal that mTERF18 mutations lead to severely undifferentiated embryos, resulting in abortive phenotypes. Early kernel exhibits abnormal basal endosperm transfer layer and a significant reduction in both starch and protein accumulation in mterf18. We identify the mTERF18 gene through mapping-based cloning and validate this gene through allelic tests. mTERF18 is widely expressed across various maize tissues and encodes a highly conserved mitochondrial protein. Transcriptome data reveal that mTERF18 mutations disrupt transcriptional termination of the nad6 gene, leading to undetectable levels of Nad6 protein and reduced complex I assembly and activity. Furthermore, transmission electron microscopy observation of mterf18 endosperm uncover severe mitochondrial defects. Collectively, these findings highlight the critical role of mTERF18 in mitochondrial gene transcription termination and its pivotal impact on maize kernel development.

Chromatin modifications including histone acetylation play essential roles in regulating flowering. The CBP/p300 family HISTONE ACETYLTRANSFERASE 1 (HAC1), which mediates histone acetylation, promotes the process of floral transition; however, the precise mechanism remains largely unclear. Specifically, how HAC1 is involved in the flowering regulatory network and which genes are the direct targets of HAC1 during flowering regulation are still unknown. In this study, we elucidated the critical function of HAC1 in promoting flowering via exerting active epigenetic markers at two key floral integrators, FT and SOC1, thereby regulating their expression to trigger the flowering process. We show that HAC1 physically interacts with CONSTANS (CO) in vivo and in vitro. Chromatin immunoprecipitation results indicate that HAC1 directly binds to the FT and SOC1 loci. Loss of HAC1 impairs CO-mediated transcriptional activation of FT and SOC1 in promoting flowering. Moreover, CO mutation leads to the decreased enrichment of HAC1 at FT and SOC1, indicating that CO recruits HAC1 to FT and SOC1. Finally, HAC1, as well as CO, is required for the elevated histone acetylation level at FT and SOC1. Taken together, our finding reveals that HAC1-mediated histone acetylation boots flowering via a CO-dependent activation of FT and SOC1.

The QTL by environment interaction (Q×E) effect is hard to detect because there are no effective ways to control the genomic background. In this study, we propose a novel linear mixed model that simultaneously analyzes data from multiple environments to detect Q×E interactions. This model incorporates two different kinship matrices derived from the genome-wide markers to control both main and interaction polygenic background effects. Simulation studies demonstrate that our approach is more powerful than the meta-analysis and inclusive composite interval mapping methods. We further analyze four agronomic traits of rice across four environments. A main effect QTL is identified for 1000-grain weight (KGW), while no QTLs are found for tiller number. Additionally, a large QTL with a significant Q×E interaction is detected on chromosome 7 affecting grain number, yield, and KGW. This region harbors two important genes, PROG1 and Ghd7. Furthermore, we apply our mixed model to analyze lodging in barley across six environments. The six regions exhibiting Q×E interaction effects identified by our approach overlap with the SNPs previously identified using EM and MCMC-based Bayesian methods, further validating the robustness of our approach. Both simulation studies and empirical data analyses show that our method outperformed all other methods compared.

The crop yields achieved through traditional plant breeding techniques appear to be nearing a plateau. Therefore, it is essential to accelerate advancements in photosynthesis, the fundamental process by which plants convert light energy into chemical energy, to further enhance crop yields. Research focused on improving photosynthesis holds significant promise for increasing sustainable agricultural productivity and addressing challenges related to global food security. This review examines the latest advancements and strategies aimed at boosting crop yields by enhancing photosynthetic efficiency. There has been a linear increase in yield over the years in historically released germplasm selected through traditional breeding methods, and this increase is accompanied by improved photosynthesis. We explore various aspects of the light reactions designed to enhance crop yield, including light harvest efficiency through smart canopy systems, expanding the absorbed light spectrum to include far-red light, optimizing non-photochemical quenching, and accelerating electron transport flux. At the same time, we investigate carbon reactions that can enhance crop yield, such as manipulating Rubisco activity, improving the Calvin-Benson-Bassham (CBB) cycle, introducing CO concentrating mechanisms (CCMs) in C plants, and optimizing carbon allocation. These strategies could significantly impact crop yield enhancement and help bridge the yield gap.

Maize (Zea mays) is the most widely cultivated crop in the world. Maize production is closely linked to the extensive uptake and utilization of various mineral nutrients. Potassium (K), calcium (Ca), and magnesium (Mg) are essential metallic macronutrients for plant growth and development. Sodium (Na) is an essential micronutrient for some C and CAM plants. Several metallic micronutrients like iron (Fe), manganese (Mn), and zinc (Zn) serve as enzyme components or co-factors in plant cells. Maize has to face the combined ion stress conditions in the natural environment. The limited availability of these nutrients in soils restricts maize production. In saline land, excessive Na could inhibit the uptake of mineral elements. Additionally, aluminum (Al) and heavy metal cadmium (Cd) and lead (Pb) in soils are toxic to maize and pose a threat to food security. Thus, plants must evolve complex mechanisms to increase nutrient uptake and utilization while restraining harmful elements. This review summarizes the research progress on the uptake and transport of metal ions in maize, highlights the regulation mechanism of metal ion transporters under stress conditions, and discusses the future challenges for the improvement of maize with high nutrient utilization efficiency (NUE).

Hereditary spastic paraplegias (HSPs) refer to a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by the degeneration of motor neurons. To date, a significant number of patients still have not received a definite genetic diagnosis. Therefore, identifying unreported causative genes continues to be of great importance. Here, we perform whole exome sequencing in a cohort of Chinese HSP patients. Three homozygous variants (p.L604W, p.S517F, and p.T984A) within the sterol regulatory element-binding factor 2 (SREBF2) gene are identified in one autosomal recessive family and two sporadic patients, respectively. Co-segregation is confirmed by Sanger sequencing in all available members. The three variants are rare in the public or in-house database and are predicted to be damaging. The biological impacts of variants in SREBF2 are examined by functional experiments in patient-derived fibroblasts and Drosophila. We find that the variants upregulate cellular cholesterol due to the overactivation of SREBP2, eventually impairing the autophagosomal and lysosomal functions. The overexpression of the mature form of SREBP2 leads to locomotion defects in Drosophila. Our findings identify SREBF2 as a causative gene for HSP and highlight the impairment of cholesterol as a critical pathway for HSP.

Reactive oxygen species (ROS) and nitric oxide (NO) are two critical classes of signaling molecules that regulate plant development and stress responses. The intracellular level of S-nitrosoglutathione (GSNO), a major bioactive NO species, is regulated by the highly conserved GSNO reductase (GSNOR). However, the molecular mechanisms underlying ROS-mediated regulation of GSNOR remain largely unclear. Here, we show that HO negatively regulates the activity of GSNOR1 during ovule development in Arabidopsis. S-sulfenylation of GSNOR1 at Cys-284 inhibits its enzymatic activity. A GSNOR1 mutation causes a reduction of the total SNO level in pistils, thereby disrupting NO homeostasis and eventually leading to defective ovule development. These findings illustrate a unique mechanism by which ROS regulates ovule development through S-sulfenylation-mediated inhibition of the GSNOR activity, thereby establishing a molecular link between ROS and NO signaling pathways in reproductive development.

Temperature fluctuations challenge ectothermic species, particularly tropical fish dependent on external temperatures for physiological regulation. However, the molecular mechanisms through which low-temperature stress impacts immune responses in these species, especially in relation to chromatin accessibility and epigenetic regulation, remain poorly understood. In this study, we investigate chromatin and transcriptional changes in the head kidney and thymus tissues of Nile tilapia (Oreochromis niloticus), a tropical fish of significant economic importance, under cold stress. By analyzing cis-regulatory elements in open chromatin regions and their associated transcription factors (TFs), we construct a comprehensive transcriptional regulatory network (TRN) governing immune responses, including DNA damage-induced apoptosis. Our analysis identifies 119 TFs within the TRN, with Stat1 emerging as a central hub exhibiting distinct binding dynamics under cold stress, as revealed by footprint analysis. Overexpression of Stat1 in immune cells leads to apoptosis and increases the expression of apoptosis-related genes, many of which contain Stat1 binding sites in their regulatory regions, emphasizing its critical role in immune cell survival during cold stress. These results provide insights into the transcriptional and epigenetic regulation of immune responses to cold stress in tilapia and highlight Stat1 as a promising target for enhancing cold tolerance in tropical fish species.

Chromosomal rearrangements (CRs) often cause phenotypic variations. Although several major rearrangements have been identified in Triticeae, a comprehensive study of the order, timing, and breakpoints of CRs has not been conducted. Here, we reconstruct high-quality ancestral genomes for the most recent common ancestor (MRCA) of the Triticeae, and the MRCA of the wheat lineage (Triticum and Aegilops). The protogenes of MRCA of the Triticeae and the wheat lineage are 22,894 and 29,060, respectively, which were arranged in their ancestral order. By partitioning modern Triticeae chromosomes into sets of syntenic regions and linking each to the corresponding protochromosomes, we revisit the rye chromosome structural evolution and propose alternative evolutionary routes. The previously identified 4L/5L reciprocal translocation in rye and Triticum urartu are found to have occurred independently and are unlikely the result of chromosomal introgression following distant hybridization. We also clarify that the 4AL/7BS translocation in tetraploid wheat was a bidirectional rather than unidirectional translocation event. Lastly, we identify several breakpoints in protochromosomes that independently reoccur following Triticeae evolution, representing potential CR hotspots. This study demonstrates that these reconstructed ancestral genomes can serve as special comparative references and facilitate a better understanding of the evolution of structural rearrangements in Triticeae.

Acral melanoma, the most common melanoma subtype in East Asia, is associated with a poor prognosis. This study aims to comprehensively analyze the genomic characteristics of acral melanoma in East Asians. We conduct whole-genome sequencing of 55 acral melanoma tumors and perform data mining with relevant clinical data. Our findings reveal a unique mutational profile in East Asian acral melanoma, characterized by fewer point mutations and structural variations, a higher prevalence of NRAS mutations, and a lower frequency of BRAF mutations compared to patients of European descent. Notably, we identify previously underestimated ultraviolet radiation signatures and their significant association with BRAF and NRAS mutations. Structural rearrangement signatures indicate distinct mutational processes in BRAF-driven versus NRAS-driven tumors. We also find that homologous recombination deficiency with MAPK pathway mutations correlated with poor prognosis. The structural variations and amplifications in EP300, TERT, RAC1, and LZTR1 point to potential novel therapeutic targets tailored to East Asian populations. The high prevalence of whole-genome duplication events in BRAF/NRAS-mutated tumors suggests a synergistic carcinogenic effect that warrants further investigation. In summary, our study provides important insights into the genetic underpinnings of acral melanoma in East Asians, creating opportunities for targeted therapies.

Ferroptosis, a type of programmed cell death, represents a distinct paradigm in cell biology. It is characterized by the iron-dependent accumulation of reactive oxygen species, which induce lipid peroxidation (LPO), and is orchestrated by the interplay between iron, lipid peroxides, and glutathione. In this review, we emphasize the frequently overlooked role of iron in LPO beyond the classical iron-driven Fenton reaction in several crucial processes that regulate cellular iron homeostasis, including iron intake and export as well as ferritinophagy, and the emerging roles of endoplasmic reticulum-resident flavoprotein oxidoreductases, especially P450 oxidoreductases, in modulating LPO. We summarize how various types of fatty acids (FAs), including saturated, monounsaturated, and polyunsaturated FAs, differentially influence ferroptosis when incorporated into phospholipids. Furthermore, we highlight the therapeutic potential of targeting LPO to mitigate ferroptosis and discuss the regulatory mechanisms of endogenous lipophilic radical-trapping antioxidants that confer resistance to ferroptosis, shedding light on therapeutic avenues for ferroptosis-associated diseases.

Small regulatory RNAs (sRNAs) are essential regulators of gene expression across a wide range of organisms to precisely modulate gene activity based on sequence-specific recognition. In model plants like Arabidopsis thaliana, extensive research has primarily concentrated on 21 to 24-nucleotide (nt) sRNAs, particularly microRNAs (miRNAs). Recent advancements in cell and tissue isolation techniques, coupled with advanced sequencing technologies, are revealing a diverse array of preciously uncharacterized sRNA species. These include previously novel structural RNA fragments as well as numerous cell- and tissue-specific sRNAs that are active during distinct developmental stages, thereby enhancing our understanding of the precise and dynamic regulatory roles of sRNAs in plant development regulation. Additionally, a notable feature of sRNAs is their capacity for amplification and movement between cells and tissues, which facilitates long-distance communication-an adaptation critical to plants due to their sessile nature. In this review, we will discuss the classification and mechanisms of action of sRNAs, using legumes as a primary example due to their essential engagement for the unique organ establishment of root nodules and long-distance signaling, and further illustrating the potential applications of sRNAs in modern agricultural breeding and environmentally sustainable plant protection strategies.

Spermiogenesis is an indispensable process occurring during the later stages of spermatogenesis. Despite multiple proteins being associated with spermiogenesis, the molecular mechanisms that control spermiogenesis remain poorly characterized. In this study, we show that 1700030J22Rik is exclusively expressed in the testis of mice and investigate its roles in spermiogenesis using genetic and proteomic approaches. The deficiency in 1700030J22Rik in male mice results in severe subfertility, characterized by a substantial decrease in sperm concentration, motility, and abnormalities in the flagella. Furthermore, 1700030J22RIK interacts with the A-kinase-anchoring protein AKAP3, and 1700030J22Rik knockout decreases AKAP3 and AKAP4 protein levels. Additionally, the absence of 1700030J22RIK alters spermatozoal levels of the subunits of protein kinase A, leading to reduced protein phosphorylation and impaired sperm motility. This study reveals that 1700030J22Rik plays a crucial role in the organization of sperm morphology and function in mice.

Salt stress significantly inhibits crop growth and development, and mitigating this can enhance salt tolerance in various crops. Previous studies have shown that regulating saccharide biosynthesis is a key aspect of plant salt tolerance; however, the underlying molecular mechanisms remain largely unexplored. In this study, we demonstrate that overexpression of a salt-inducible galactinol synthase gene, ZmGolS1, alleviates salt-induced growth inhibition, likely by promoting raffinose synthesis. Additionally, we show that natural variation in ZmGolS1 transcript levels contributes to the diversity of raffinose content and salt tolerance in maize. We further reveal that ZmRR18, a type-B response regulator transcription factor, binds to the AATC element in the promoter of ZmGolS1, with this binding increases the transcript levels of ZmGolS1 under salt conditions. Moreover, a single nucleotide polymorphism (termed SNP-302T) within the ZmGolS1 promoter significantly reduces its binding affinity for ZmRR18, resulting in decreased ZmGolS1 expression and diminished raffinose content, ultimately leading to a salt-hypersensitive phenotype. Collectively, our findings reveal the molecular mechanisms by which the ZmRR18-ZmGolS1 module enhances raffinose biosynthesis, thereby promoting maize growth under salt conditions. This research provides important insights into salt tolerance mechanisms associated with saccharide biosynthesis and identifies valuable genetic loci for breeding salt-tolerant maize varieties.

Mutations in the Rhodopsin (RHO) gene are the main cause of autosomal dominant retinitis pigmentosa (adRP), 84% of which are pathogenic gain-of-function point mutations. Treatment strategies for adRP typically involve silencing or ablating the pathogenic allele, while normal RHO protein replacement has no meaningful therapeutic benefit. Here, we present an adenine base editor (ABE)-mediated therapeutic approach for adRP caused by RHO point mutations in vivo. The correctable pathogenic mutations are screened and verified, including T17M, Q344ter, and P347L. Two adRP animal models are created carrying the class 1 (Q344ter) and class 2 (T17M) mutations, and dual AAV-delivered ABE can effectively repair both mutations in vivo. The early intervention of ABE8e efficiently corrects the Q344ter mutation that causes a severe form of adRP, delays photoreceptor death, and restores retinal function and visual behavior. These results suggest that ABE is a promising alternative to treat RHO mutation-associated adRP. Our work provides an effective spacer-mediated point mutation correction therapy approach for dominantly inherited ocular disorders.

It has recently become evident that the de novo emergence of genes is widespread and documented for a variety of organisms. De novo genes frequently emerge in proximity to existing genes, forming gene overlaps. Here, we present an analysis of the evolutionary history of a putative de novo gene, lawc, which overlaps with the conserved Trf2 gene, which encodes a general transcription factor in Drosophila melanogaster. We demonstrate that lawc emerged approximately 68 million years ago in the 5'-untranslated region of Trf2 and displays an extensive spatiotemporal expression pattern. One of the most remarkable features of the lawc evolutionary history is that its emergence was facilitated by the engagement of Drosophilidae-specific short highly conserved regions located in Trf2 introns. This represents a unique example of putative de novo gene birth involving conserved DNA regions localized in introns of conserved gene. The observed lawc expression pattern may be due to overlap of lawc with the 5'-untranslated region of Trf2. This study not only enriches our understanding of gene evolution but also highlights the complex interplay between genetic conservation and innovation.

Saline-alkali soil severely reduces the productivity of crops, including maize (Zea mays). Although several genes associated with saline-alkali tolerance have been identified in maize, the underlying regulatory mechanism remains elusive. Here, we report a direct link between colonization by arbuscular mycorrhizal fungi (AMF) and saline-alkali tolerance in maize. We identify s75, a natural maize mutant that cannot survive under moderate saline-alkali soil conditions or establish AM symbioses. The saline-alkali hypersensitive phenotype of s75 is caused by a 1340-bp deletion in Zm00001d033915, designated as ZmL75. This gene encodes a glycerol-3-phosphate acyltransferase localized in the endoplasmic reticulum, and is responsible for AMF colonization. ZmL75 expression levels in roots correspond with the root length colonization (RLC) rate during early vegetative development. Notably, the s75 mutant line shows a complete loss of AMF colonization, along with alterations in the diversity and structure of its root fungal microbiota. Conversely, overexpression of ZmL75 increases the RLC rate and enhances tolerance to saline-alkali soil conditions. These results suggest that ZmL75 is required for symbiosis with AMF, which directly improves saline-alkali tolerance. Our findings provide insights into maize-AMF interactions and offer a potential strategy for maize improvement.

Plant synthetic biology has emerged as a transformative field in agriculture, offering innovative solutions to enhance food security, provide resilience to climate change, and transition to sustainable farming practices. By integrating advanced genetic tools, computational modeling, and systems biology, researchers can precisely modify plant genomes to enhance traits such as yield, stress tolerance, and nutrient use efficiency. The ability to design plants with specific characteristics tailored to diverse environmental conditions and agricultural needs holds great potential to address global food security challenges. Here we highlight recent advancements and applications of plant synthetic biology in agriculture, focusing on key areas such as photosynthetic efficiency, nitrogen fixation, drought tolerance, pathogen resistance, nutrient use efficiency, biofortification, climate resilience, microbiology engineering, synthetic plant genomes, and the integration of artificial intelligence (AI) with synthetic biology. These innovations aim to maximize resource use efficiency, reduce reliance on external inputs, and mitigate environmental impacts associated with conventional agricultural practices. Despite challenges related to regulatory approval and public acceptance, the integration of synthetic biology in agriculture holds immense promise for creating more resilient and sustainable agricultural systems, contributing to global food security and environmental sustainability. Rigorous multi-field testing of these approaches will undoubtedly be required to ensure reproducibility.