DNA methylation is an important epigenetic mark involved in many biological processes. The genome of the climacteric tomato fruit undergoes a global loss of DNA methylation due to active DNA ...demethylation during the ripening process. It is unclear whether the ripening of other fruits is also associated with global DNA demethylation. We characterized the single-base resolution DNA methylomes of sweet orange fruits. Compared with immature orange fruits, ripe orange fruits gained DNA methylation at over 30,000 genomic regions and lost DNA methylation at about 1,000 genomic regions, suggesting a global increase in DNA methylation during orange fruit ripening. This increase in DNA methylation was correlated with decreased expression of DNA demethylase genes. The application of a DNA methylation inhibitor interfered with ripening, indicating that the DNA hypermethylation is critical for the proper ripening of orange fruits. We found that ripening-associated DNA hypermethylation was associated with the repression of several hundred genes, such as photosynthesis genes, and with the activation of hundreds of genes, including genes involved in abscisic acid responses. Our results suggest important roles of DNA methylation in orange fruit ripening.
Salt and drought stress signal transduction consists of ionic and osmotic homeostasis signaling pathways, detoxification (i.e., damage control and repair) response pathways, and pathways for growth ...regulation. The ionic aspect of salt stress is signaled via the SOS pathway where a calcium-responsive SOS3-SOS2 protein kinase complex controls the expression and activity of ion transporters such as SOS1. Osmotic stress activates several protein kinases including mitogen-activated kinases, which may mediate osmotic homeostasis and/or detoxification responses. A number of phospholipid systems are activated by osmotic stress, generating a diverse array of messenger molecules, some of which may function upstream of the osmotic stress-activated protein kinases. Abscisic acid biosynthesis is regulated by osmotic stress at multiple steps. Both ABA-dependent and -independent osmotic stress signaling first modify constitutively expressed transcription factors, leading to the expression of early response transcriptional activators, which then activate downstream stress tolerance effector genes.
Biosyntheses of proteins, nucleotides and fatty acids, are essential for the malignant proliferation and survival of cancer cells. Cumulating research findings show that amino acid restrictions are ...potential strategies for cancer interventions. Meanwhile, dietary strategies are popular among cancer patients. However, there is still lacking solid rationale to clarify what is the best strategy, why and how it is. Here, integrated analyses and comprehensive summaries for the abundances, signalling and functions of amino acids in proteomes, metabolism, immunity and food compositions, suggest that, intermittent dietary lysine restriction with normal maize as an intermittent staple food for days or weeks, might have the value and potential for cancer prevention or therapy. Moreover, dietary supplements were also discussed for cancer cachexia including dietary immunomodulatory.
Summary
We developed simplified single transcriptional unit (SSTU) CRISPR systems for multiplex gene editing in rice using FnCpf1, LbCpf1 or Cas9, in which the nuclease and its crRNA array are ...co‐expressed from a single Pol II promoter, without any additional processing machinery. Our SSTU systems are easy to construct and effective in mediating multiplex genome editing.
We developed the simplified single transcriptional unit (SSTU) CRISPR systems for multiplex gene editing in rice using FnCpf1, LbCpf1 or Cas9, in which the nuclease and its crRNA array are co‐expressed from single Pol II promoter, without any additional processing machinery. SSTU systems are simple and effective in multiplex genome editing.
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•Combined effects of MPs and BHA on zebrafish embryos/larvae were evaluated.•MPs promoted the accumulation of BHA in zebrafish larvae.•MPs enhanced the toxicity of BHA in larvae ...development.•Coexposure disturbed arachidonic acid, glycerophospholipid, and lipids metabolism.
Coexposure of MPs and other contaminants adsorbed from the environment has raised many attentions, but the understanding of the combined effects of MPs and plastic additives are limited. Butylated hydroxyanisole (BHA), a widely used synthetic phenolic antioxidant in plastics, has gained high concerns due to their unintended environmental release and potential threat to aquatic organisms. This study was conducted to reveal the influences of MPs on the bioaccumulation and developmental toxicity of BHA in zebrafish larvae. As a result, MPs promoted the accumulation of BHA in zebrafish larvae and enhanced the toxicity of BHA in larvae development manifested by reduced hatching rates, increased malformation rates and decreased calcified vertebrae. Although the concentration of MPs was not sufficient to cause obvious developmental toxicity, the impacts of MPs on thyroid hormones status might contribute to the aggravated join toxicity. The metabolomic mechanism was revealed to be that the coexposure of BHA and MPs affected the development of zebrafish larvae via disturbing the metabolism of arachidonic acid, glycerophospholipid, and lipids. Our results emphasized that MPs, even at the nontoxic concentrations, in combination with additives caused health risk that should not be ignored.
TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved ...amino acids and targets a specific base pair by using two hypervariable residues known as repeat variable diresidues (RVDs) at positions 12 and 13. Here, we report the crystal structures of an 11.5-repeat TAL effector in both DNA-free and DNA-bound states. Each TAL repeat comprises two helices connected by a short RVD-containing loop. The 11.5 repeats form a right-handed, superhelical structure that tracks along the sense strand of DNA duplex, with RVDs contacting the major groove. The 12th residue stabilizes the RVD loop, whereas the 13th residue makes a base-specific contact. Understanding DNA recognition by TAL effectors may facilitate rational design of DNA-binding proteins with biotechnological applications.
Long non-coding RNAs (lncRNAs) function as critical regulators to participate in tumor progression and metastasis. However, their roles in non-small cell lung cancer (NSCLC) are poorly understood. In ...this study, we found that the expression of the lncRNA linc00460 is significantly upregulated in NSCLC tumors and associated with poor prognosis for NSCLC patients, implying that linc00460 is important for lung cancer development. The accurate transcription initiation and termination sites of linc00460 were then identified by rapid-amplification of cDNA ends (RACE) technologies, and the sequencing data demonstrated that linc00460, predominantly located in the cytoplasm of lung cancer cells, is a novel transcript variant. Functional studies through gain- and loss-of-function strategies showed that linc00460 promotes cell migration and invasion through inducing epithelial-mesenchymal transition in lung cancer cells, whereas it has no effect on cell proliferation. The mechanism investigations through RNA pull-down assay and mass spectrometry identified that hnRNP K physically interacts with linc00460, and it also participates in cell migration and invasion. Therefore, our findings suggest that linc00460 acts as an oncogene in NSCLC to promote cell migration and highlight the potential prognostic and therapeutic values of linc00460 for NSCLC patients.
•Upregulation of the lncRNA linc00460 expression in NSCLC tumors.•Linc00460 promotes cell migration and invasion through inducing EMT in lung cancer cells.•hnRNP K physically interacts with linc00460 and participate in cell migration.
Dear Editor, Rice （Oryza sativa） is the staple food for more than half of the world＇s population. Technologies enabling precise and efficient DNA knock-in or replacement, hereinafter referred to as ...KI, have the potential to revolutionize the generation of crops by precision molecular breeding.
Recent studies have revealed that microRNAs (miRNAs) regulate plant adaptive responses to nutrient deprivation. However, the functional significance of miRNAs in adaptive responses to nitrogen (N) ...limitation remains to be explored. The Arabidopsis miR169 was strongly down-regulated, whereas its targets, NFYA (Nuclear Factor Y, subunit A) family members, were strongly induced by nitrogen N starvation. Analysis of the expression of miR169 precursors showed that MIR169a was substantially down-regulated in both roots and shoots by N starvation. Accumulation of the NFYA family members was suppressed in transgenic Arabidopsis with constitutive expression of MIR169a. Transgenic Arabidopsis plants overexpressing MIR169a accumulated less N and were more sensitive to N stress than the wild type. N sensitivity of 35S::MIR169a might be attributable to impaired uptake systems. These results provide evidence that miRNAs have functional roles in helping plants to cope with fluctuations in N availability in the soil.
Maintaining proper DNA methylation levels in the genome requires active demethylation of DNA. However, removing the methyl group from a modified cytosine is chemically difficult and therefore, the ...underlying mechanism of demethylation had remained unclear for many years. The discovery of the first eukaryotic DNA demethylase, Arabidopsis thaliana REPRESSOR OF SILENCING 1 (ROS1), led to elucidation of the 5‐methylcytosine base excision repair mechanism of active DNA demethylation. In the 20 years since ROS1 was discovered, our understanding of this active DNA demethylation pathway, as well as its regulation and biological functions in plants, has greatly expanded. These exciting developments have laid the groundwork for further dissecting the regulatory mechanisms of active DNA demethylation, with potential applications in epigenome editing to facilitate crop breeding and gene therapy.
Active DNA demethylation is critical for maintaining correct DNA methylation patterns in eukaryotic genomes. This review summarizes the main advances in plant active DNA demethylation, focusing on the base excision repair mechanism, regulatory pathways, and the function of active DNA demethylation during plant growth and development, and plant‐environment interactions
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