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A common mRNA modification is 5-methylcytosine (m5C), whose role in gene-transcript processing and cancer remains unclear. Here, we identify serine/arginine-rich splicing factor 2 (SRSF2) as a reader of m5C and impaired SRSF2 m5C binding as a potential contributor to leukemogenesis. Structurally, we identify residues involved in m5C recognition and the impact of the prevalent leukemia-associated mutation SRSF2P95H. We show that SRSF2 binding and m5C colocalize within transcripts. Furthermore, knocking down the m5C writer NSUN2 decreases mRNA m5C, reduces SRSF2 binding, and alters RNA splicing. We also show that the SRSF2P95H mutation impairs the ability of the protein to read m5C-marked mRNA, notably reducing its binding to key leukemia-related transcripts in leukemic cells. In leukemia patients, low NSUN2 expression leads to mRNA m5C hypomethylation and, combined with SRSF2P95H, predicts poor outcomes. Altogether, we highlight an unrecognized mechanistic link between epitranscriptomics and a key oncogenesis driver.
Assuntos
Leucemia , Síndromes Mielodisplásicas , Neoplasias , Metilação de RNA , Fatores de Processamento de Serina-Arginina , Humanos , Leucemia/genética , Síndromes Mielodisplásicas/genética , Neoplasias/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Fatores de Processamento de Serina-Arginina/genética , Metilação de RNA/genéticaRESUMO
Herbivore-associated molecular patterns (HAMPs) enable plants to recognize herbivores and may help plants adjust their defense responses. Here, we report on herbivore-induced changes in a protein disulfide isomerase (PDI) widely distributed across arthropods. PDI from the spider mite Tetranychus evansi (TePDI), a mesophyll-feeding agricultural pest worldwide, triggered immunity in multiple Solanaceae plants. TePDI-mediated cell death in Nicotiana benthamiana required the plant signaling proteins SGT1 (suppressor of the G2 allele of skp1) and HSP90 (heat shock protein 90), but was suppressed by spider mite effectors Te28 and Te84. Moreover, PDIs from phylogenetically distinct herbivorous and nonherbivorous arthropods triggered plant immunity. Finally, although PDI-induced plant defenses impaired the performance of spider mites on plants, RNAi experiments revealed that PDI genes are essential for the survival of mites and whiteflies. Our findings indicate that plants recognize evolutionarily conserved HAMPs to activate plant defense and resist pest damage, pointing to opportunities for broad-spectrum pest management.
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Herbivoria , Tetranychidae , Animais , Isomerases de Dissulfetos de Proteínas/genética , Plantas , Nicotiana/genética , Proteínas de Plantas/genética , Tetranychidae/fisiologiaRESUMO
More than 170 different types of chemical modifications have been identified on diverse types of RNA, collectively known as the epitranscriptome. Among them, N6-methyladenine (m6A), 5-methylcytosine (m5C), N1-methyladenine (m1A), and N7-methylguanosine (m7G) as the ubiquitous post-transcriptional modification are widely involved in regulating the metabolic processes such as RNA degradation, translation, stability, and export, mediating important physiological and pathological processes such as stress regulation, immune response, development, and tumorigenesis. Recently, the regulatory role of RNA modification during developmental processes is getting more attention. Therefore, the development of low-input even single-cell and high-resolution sequencing technologies is crucial for the exploration of the regulatory roles of RNA modifications in these important biological events of trace samples.This account focuses on the roles of RNA modifications in various developmental processes. We describe the distribution characteristics of various RNA modifications, catalytic enzymes, binding proteins, and the development of sequencing technologies. RNA modification is dynamically reversible, which can be catalyzed by methyltransferases and eliminated by demethylases. RNA m6A is the most abundant post-transcriptional modification on eukaryote mRNA, which is mainly concentrated near the stop codon, and involves in RNA metabolism regulation. RNA m5C, another most studied RNA modification, has been identified in a various of organisms and RNA species, mainly enriched in the regions downstream of translation initiation sites and broadly distributes across the whole coding sequence (CDS) in mammalian mRNAs. RNA m1A, with a lower abundance than m6A, is widely distributed in various RNA types, mainly locates in the 5' untranslated region (5'UTR) of mRNA and regulates translation. RNA m7G, one of the most common RNA modifications in eukaryotes, has been identified at cap regions and internal positions of RNAs and recently gained considerable attention.Thanks to the development of sequencing technology, m6A has been found to regulate the tumorigenic process, including tumor proliferation, invasion, and metastasis by modulating oncogenes and tumor suppressor genes, and affect oocyte maturation and embryonic development through regulating maternal and zygotic genes. m5C related proteins have been identified to participate in embryonic development, plant growth, and neural stem cell differentiation in a m5C dependent manner. m1A also has been revealed to be involved in these developmental processes. m7G dysregulation mainly involves in neurodevelopmental disorders and neurodegenerative diseases.Collectively, we summarized the gradually exhibited roles of RNA methylation during development, and discussed the possibility of RNA modifications as candidate biomarkers and potential therapeutic targets. The technological development is anticipated as the major driving force to expand our knowledge in this field.
Assuntos
Metiltransferases , RNA , Animais , Metilação , RNA/genética , RNA/metabolismo , RNA Mensageiro/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Diferenciação Celular , Processamento Pós-Transcricional do RNA , Mamíferos/genética , Mamíferos/metabolismoRESUMO
Lithium niobate-on-insulator (LNOI) has recently emerged as a promising material platform for high-density and advanced photonics integrated circuits (PICs). And single-mode waveguides (SMW) are the most basic building blocks for structuring various PICs. In this paper, single-mode conditions (SMCs) for shallowly etched LNOI rib waveguides in x-cut LNOI wafer are investigated with the finite element method (FEM) in consideration of the lateral leakage and the magic width for the first time, to our best knowledge. Our results indicate that due to the lateral leakage and the magic width these shallowly etched x-cut LNOI rib waveguides have unique and complex SMCs. Our method and results provide a guidance in designing low-loss LNOI SMW and high-performance PICs.
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Symbiotic microorganisms are essential for the physiological processes of herbivorous pests, including the pear lace bug Stephanitis nashi, which is known for causing extensive damage to garden plants and fruit trees due to its exceptional adaptability to diverse host plants. However, the specific functional effects of the microbiome on the adaptation of S. nashi to its host plants remains unclear. Here, we identified significant microbial changes in S. nashi on 2 different host plants, crabapple and cherry blossom, characterized by the differences in fungal diversity as well as bacterial and fungal community structures, with abundant correlations between bacteria or fungi. Consistent with the microbiome changes, S. nashi that fed on cherry blossom demonstrated decreased metabolites and downregulated key metabolic pathways, such as the arginine and mitogen-activated protein kinase signaling pathway, which were crucial for host plant adaptation. Furthermore, correlation analysis unveiled numerous correlations between differential microorganisms and differential metabolites, which were influenced by the interactions between bacteria or fungi. These differential bacteria, fungi, and associated metabolites may modify the key metabolic pathways in S. nashi, aiding its adaptation to different host plants. These results provide valuable insights into the alteration in microbiome and function of S. nashi adapted to different host plants, contributing to a better understanding of pest invasion and dispersal from a microbial perspective.
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Wolbachia-based incompatible insect technique (IIT) and pathogen blocking technique (PBT) have been shown to be effective at protecting humans from mosquito-borne diseases in the past decades. Population suppression based on IIT and population replacement based on PBT have become major field application strategies that have continuously been improved by the translational research on Wolbachia-transinfected mosquitoes. Similarly, Wolbachia-based approaches have been proposed for the protection of plants from agricultural pests and their associated diseases. However, a bottleneck in Wolbachia-based strategies for the control of agricultural pests is the need for methods to establish Wolbachia-transinfected insect lines. As a first step in this direction, we compare field control strategies for mosquitos with the potential strategies for agricultural pests based on Wolbachia. Our results show that there is a critical need for establishing productive insect lines and accumulating field test data.
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Aedes , Wolbachia , Humanos , Animais , Dinâmica PopulacionalRESUMO
The endosymbiont Wolbachia manipulates host reproduction by several strategies, one of the most important of which is cytoplasmic incompatibility (CI). CI can be rescued when Wolbachia-infected males mate with females infected with the same Wolbachia strain. However, the potential rescue mechanism of CI in the small brown planthopper Laodelphax striatellus is unclear. In this study, comparative transcriptome analysis was applied to explore the effect of Wolbachia on L. striatellus eggs. A total of 1387 differentially expressed genes were identified. RNA interference of 7 Wolbachia-upregulated key planthopper genes reduced egg reproduction, suggesting that Wolbachia might improve fecundity in L. striatellus by affecting these 7 genes. Suppressing the expression of another upregulated gene, NDUFA8 (encoding NADH dehydrogenase [ubiquinone] 1 α subcomplex subunit 8-like) by RNA interference significantly increased the mortality of early embryos without affecting the number of deposited eggs. Wolbachia infection upregulated the mRNA level of NDUFA8, and dsNDUFA8 treatment of Wolbachia-infected females recreated CI-like symptoms, suggesting that NDUFA8 is associated with the rescue phenotype. Because all L. striatellus populations worldwide are infected with Wolbachia, NDUFA8 is a potential pest control target.
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Hemípteros , Wolbachia , Feminino , Masculino , Animais , Wolbachia/genética , Hemípteros/genética , Hemípteros/metabolismo , Fertilidade , Reprodução , Perfilação da Expressão GênicaRESUMO
Endosymbionts can strongly affect bacterial microbiota in pests. The white-backed planthopper Sogatella furcifera, a notorious pest in rice, is usually co-infected with Cardinium and Wolbachia, but the effects of these endosymbionts together or individually on the host microbiome and fecundity are unclear. Here, we established three S. furcifera lines (Cardinium and Wolbachia double-infected, Cardinium single-infected, and both-uninfected lines) backcrossed to a common nuclear background and found that single and double infections reduced bacterial diversity and changed bacterial community structure across nymph and adult stages and across adult tissues. The endosymbionts differed in densities between adults and nymphs as well as across adult tissues, with the distribution of Cardinium affected by Wolbachia. Both the single infection and particularly the double infection reduced host fecundity. Lines also differed in levels of metabolites, some of which may influence fecundity (e.g., arginine biosynthesis and nicotinamide metabolism). Cardinium in the single-infected line upregulated metabolic levels, while Wolbachia in the double-infected line appeared to mainly downregulate them. Association analysis pointed to possible connections between various bacteria and differential metabolites. These results reveal that Cardinium by itself and in combination with Wolbachia affect bacterial microbiota and levels of metabolites, with likely effects on host fecundity. Many of the effects of these metabolically limited endosymbionts that are dependent on the hosts may be exerted through manipulation of the microbiome. IMPORTANCE Endosymbionts can profoundly affect the nutrition, immunity, development, and reproduction of insect hosts, but the effects of multiple endosymbiont infections on microbiota and the interaction of these effects with insect host fitness are not well known. By establishing S. furcifera lines with different endosymbiont infection status, we found that Cardinium and the combined Cardinium + Wolbachia infections differentially reduced bacterial diversity as well as changing bacterial community structure and affecting metabolism, which may connect to negative fitness effects of the endosymbionts on their host. These results established the connections between reduced bacterial diversity, decreased fecundity and metabolic responses in S. furcifera.
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Hemípteros , Microbiota , Wolbachia , Animais , Fertilidade , Reprodução , Bacteroidetes , NinfaRESUMO
This study explored the discrepancy in the detoxification effects of different exogenous selenium (Se) species in cadmium (Cd)-contaminated soil to provide a scientific basis for the control of Cd pollution in the soil and the safe production of crops. A pot experiment was conducted to compare the effects of different concentrations (0, 0.5, 1.0, and 2.5 mg·kg-1) of selenite and selenate on the growth (root length, shoot height, biomass, and photosynthetic parameters), uptake, and translocation of Cd on pak choi in Cd-contaminated soil. The results indicated that the detoxification effect of a low Se concentration (≤1.0 mg·kg-1) treatment on Cd was better than that with a high Se concentration (2.5 mg·kg-1) treatment, and the selenite treatment demonstrated a greater detoxification effect on Cd than the corresponding selenate treatment. Meanwhile, the application of low-concentration selenite and selenate both increased the SPAD value, Pn, Gs, Ci, biomass, and shoot length of the pak choi, and the 1.0 mg·kg-1 selenite treatment had the most significant (P<0.05) effect (except Ci). Nevertheless, the photosynthetic parameters of the pak choi under the high-concentration Se were significantly lower than those under the low Se concentration treatment (except Tr, P<0.05). Compared with the treatment without Se (control), the uptake of Cd in the pak choi was reduced under different Se treatments. Compared with the control, the Cd concentration in the shoots of the pak choi treated with 1.0 mg·kg-1 of selenite and selenate decreased by 40.0% and 20.5% (P<0.05), respectively. In addition, the translocation of Cd from the root to the shoot was significantly reduced under the 0.5 mg·kg-1 selenate treatment, while the high-concentration treatments of either exogenous Se promoted the translocation of Cd. Overall, applying the appropriate amount of exogenous Se could promote the photosynthesis and biomass of pak choi, and reduce the accumulation of Cd in pak choi. Therefore, the 1.0 mg·kg-1 selenite treatment is recommended for the control and safe utilization of Cd in Cd-contaminated soil.
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Brassica , Selênio , Poluentes do Solo , Cádmio/toxicidade , Ácido Selênico , Solo , Poluentes do Solo/análiseRESUMO
The study aimed to find out the dynamic changes of selenium (Se) uptake with crops growing and to provide better understanding on the translocation of Se in soil-plant system. Pot experiments and laboratory analysis were carried out, in which 6 crops were planted for eight weeks in the soils treated with selenite and selenate. The results showed that there was a significant difference in the plant dynamic uptake pattern for selenite and selenate. Se concentration in shoots and roots of all tested plants continuously declined with growth since the third week after planting for selenate treatment; while Se concentration in roots of plants gradually increased with the growth, and that for shoots firstly increased and then leveled off or decreased for selenite treatment. Crops could accumulate Se throughout the whole growing period, while 80% of the Se in plants was uptaken in the first 6 weeks. Among the 6 tested plants, the Se concentration in the shoots and roots of mustard was the highest, followed by the shoots of wheat for selenate treatment. The Se concentration in shoots of carrot was the highest, while that in roots was the lowest for selenite treatment. For the same Se treatment, the Se concentrations in both roots and shoots of broccoli, purple cabbage and flowering Chinese cabbage were similar. Broccoli, purple cabbage, flowering Chinese cabbage, mustard and wheat had higher translocation ability to transport selenate than selenite from roots to shoots, whereas carrot had the same ability for translocating selenite and selenate. Biological dilution affected the dynamic changes of the Se content in crops, especially for selenate treatment, and a significant negative correlation between Se concentration of plants and their biomass further verified this. However, the changes of biomass of plants with growing period couldn't explain the total inverse dynamic uptake pattern for selenite and selenate. A significant positive correlation was observed between Se accumulations amount in six crops with available Se changes in soil during the corresponding growing period for selenate treatment, while no such correlation was found for selenite treatment. Se accumulation in crops grown on selenite-treated soil accounted for 0.5%-18.1% of soil available Se, whereas that in selenate treatment was 1.1-4.5 times of soil available Se except for carrot. In conclusion, the dynamic changes of Se uptake with crop growth were the comprehensive results of the absorption and transport capacity of crops, Se availability in soil and biological dilution. It should be considered as a whole in the selenium biofortification.
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Produtos Agrícolas/metabolismo , Selênio/metabolismo , Brassica , Daucus carota , Ácido Selênico/metabolismo , Ácido Selenioso/metabolismo , Solo , TriticumRESUMO
The effect of the change in concentration and valence of iron ion on the ANAMMOX sludge activity was studied by inoculating ANAMMOX sludge. The concentration experimental results showed that the ANAMMOX sludge activity was stimulated and gradually increased when the influent iron ion concentration increased from 0 to 5 mg x L(-1). Iron hydroxide precipitate was formed with the pH value increased due to the alkalinity of the ANAMMOX product when the influent iron ion concentration was higher than 5 mg x L(-1), while the biological activity was not inhibited. There was no significant difference in the effects of the concentration change of iron ions with different valence effects on the ANAMMOX sludge activity. The long-term experimental results showed that the nitrogen removal rate (as N) of anammox reactor R1 was increased from 0.28 kg x (m3 x d)(-1) to 0.65 kg x (m3 x d)(-1) with Fe2+ in influent, which was 1.28 times as high as that in the ANAMMOX reactor R2 containing Fe3+ in influent, after 71 cycles of cultivation. Therefore, Fe2+ could better meet the growth needs of ANAMMOX bacteria. The results also showed that Fe3+ easily led to the excessive conversion of ammonia in the ANAMMOX reactor. The conversion ratio between nitrate and ammonia was 1.17 in reactor R2, which was significantly lower than that in the reactor R1, with a conversion ratio between nitrate and ammonia of 1.24.