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1.
Nanomaterials (Basel) ; 14(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38470773

RESUMO

Aluminum-ion batteries (AIBs) have become a research hotspot in the field of energy storage due to their high energy density, safety, environmental friendliness, and low cost. However, the actual capacity of AIBs is much lower than the theoretical specific capacity, and their cycling stability is poor. The exploration of energy storage mechanisms may help in the design of stable electrode materials, thereby contributing to improving performance. In this work, molybdenum disulfide (MoS2) was selected as the host material for AIBs, and carbon nanofibers (CNFs) were used as the substrate to prepare a molybdenum disulfide/carbon nanofibers (MoS2/CNFs) electrode, exhibiting a residual reversible capacity of 53 mAh g-1 at 100 mA g-1 after 260 cycles. The energy storage mechanism was understood through a combination of electrochemical characterization and first-principles calculations. The purpose of this study is to investigate the diffusion behavior of ions in different channels in the host material and its potential energy storage mechanism. The computational analysis and experimental results indicate that the electrochemical behavior of the battery is determined by the ion transport mechanism between MoS2 layers. The insertion of ions leads to lattice distortion in the host material, significantly impacting its initial stability. CNFs, serving as a support material, not only reduce the agglomeration of MoS2 grown on its surface, but also effectively alleviate the volume expansion caused by the host material during charging and discharging cycles.

2.
Curr Biol ; 34(6): 1309-1323.e4, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38471505

RESUMO

For sexually reproducing animals, selecting optimal mates is important for maximizing reproductive fitness. In the nematode C. elegans, populations reproduce largely by hermaphrodite self-fertilization, but the cross-fertilization of hermaphrodites by males also occurs. Males' ability to recognize hermaphrodites involves several sensory cues, but an integrated view of the ways males use these cues in their native context to assess characteristics of potential mates has been elusive. Here, we examine the mate-preference behavior of C. elegans males evoked by natively produced cues. We find that males use a combination of volatile sex pheromones (VSPs), ascaroside sex pheromones, surface-associated cues, and other signals to assess multiple features of potential mates. Specific aspects of mate preference are communicated by distinct signals: developmental stage and sex are signaled by ascaroside pheromones and surface cues, whereas the presence of a self-sperm-depleted hermaphrodite is likely signaled by VSPs. Furthermore, males prefer to interact with virgin over mated, and well-fed over food-deprived, hermaphrodites; these preferences are likely adaptive and are also mediated by ascarosides and other cues. Sex-typical mate-preference behavior depends on the sexual state of the nervous system, such that pan-neuronal genetic masculinization in hermaphrodites generates male-typical social behavior. We also identify an unexpected role for the sex-shared ASH sensory neurons in male attraction to ascaroside sex pheromones. Our findings lead to an integrated view in which the distinct physical properties of various mate-preference cues guide a flexible, stepwise behavioral program by which males assess multiple features of potential mates to optimize mate preference.


Assuntos
Caenorhabditis elegans , Atrativos Sexuais , Animais , Feminino , Masculino , Caenorhabditis elegans/fisiologia , Sinais (Psicologia) , Sêmen , Comportamento Sexual Animal/fisiologia , Feromônios/fisiologia , Células Receptoras Sensoriais
3.
Small ; 20(6): e2306104, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37775948

RESUMO

Microwave absorbers with high efficiency and mechanical robustness are urgently desired to cope with more complex and harsh application scenarios. However, manipulating the trade-off between microwave absorption performance and mechanical properties is seldom realized in microwave absorbers. Here, a chemistry-tailored charge dynamic engineering strategy is proposed for sparking hetero-interfacial polarization and thus coordinating microwave attenuation ability with the interfacial bonding, endowing polymer-based composites with microwave absorption efficiency and mechanical toughness. The absorber designed by this new conceptual approach exhibits remarkable Ku-band microwave absorption efficiency (-55.3 dB at a thickness of 1.5 mm) and satisfactory effective absorption bandwidth (5.0 GHz) as well as desirable interfacial shear strength (97.5 MPa). The calculated differential charge density depicts the uneven distribution of space charge and the intense hetero-interfacial polarization, clarifying the structure-performance relationship from a theoretical perspective. This work breaks through traditional single performance-oriented design methods and ushers a new direction for next-generation microwave absorbers.

4.
bioRxiv ; 2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37066192

RESUMO

For sexually reproducing animals, selecting optimal mates is essential for maximizing reproductive fitness. Because the nematode C. elegans reproduces mostly by self-fertilization, little is known about its mate-choice behaviors. While several sensory cues have been implicated in males' ability to recognize hermaphrodites, achieving an integrated understanding of the ways males use these cues to assess relevant characteristics of potential mates has proven challenging. Here, we use a choice-based social-interaction assay to explore the ability of C. elegans males to make and optimize mate choices. We find that males use a combination of volatile sex pheromones (VSPs), ascaroside pheromones, surface-bound chemical cues, and other signals to robustly assess a variety of features of potential mates. Specific aspects of mate choice are communicated by distinct signals: the presence of a sperm-depleted, receptive hermaphrodite is likely signaled by VSPs, while developmental stage and sex are redundantly specified by ascaroside pheromones and surface-associated cues. Ascarosides also signal nutritional information, allowing males to choose well-fed over starved mates, while both ascarosides and surface-associated cues cause males to prefer virgin over previously mated hermaphrodites. The male-specificity of these behavioral responses is determined by both male-specific neurons and the male state of sex-shared circuits, and we reveal an unexpected role for the sex-shared ASH sensory neurons in male attraction to endogenously produced hermaphrodite ascarosides. Together, our findings lead to an integrated view of the signaling and behavioral mechanisms by which males use diverse sensory cues to assess multiple features of potential mates and optimize mate choice.

5.
Nat Commun ; 14(1): 320, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658169

RESUMO

Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what extent metabolomes differ between sexes. Here, using untargeted comparative metabolomics for the analysis of wildtype animals and sex determination mutants, we show that C. elegans hermaphrodites and males exhibit pervasive metabolomic differences. Several hundred small molecules are produced exclusively or in much larger amounts in one sex, including a host of previously unreported metabolites that incorporate building blocks from nucleoside, carbohydrate, lipid, and amino acid metabolism. A subset of male-enriched metabolites is specifically associated with the presence of a male germline, whereas enrichment of other compounds requires a male soma. Further, we show that one of the male germline-dependent metabolites, an unusual dipeptide incorporating N,N-dimethyltryptophan, increases food consumption, reduces lifespan, and accelerates the last stage of larval development in hermaphrodites. Our results serve as a foundation for mechanistic studies of how the genetic sex of soma and germline shape the C. elegans metabolome and provide a blueprint for the discovery of sex-dependent metabolites in other animals.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Masculino , Caenorhabditis elegans/metabolismo , Metaboloma , Proteínas de Caenorhabditis elegans/metabolismo , Metabolômica/métodos , Longevidade
6.
Artigo em Inglês | MEDLINE | ID: mdl-36361191

RESUMO

The mechanical behavior of carbonaceous mudstone deteriorates greatly when exposed to wet environments, and the precise evaluation of its slope stability has been a difficulty. This study aims to establish a numerical analysis method for the instability problems of its slopes; this method considers the effects of weathering and water-softening by establishing their mathematical expressions. The weathering and water-softening effects are reflected by variations in the mechanical properties (e.g., elastic modulus, angle of internal friction, and cohesion) of carbonaceous mudstone, with the depth following a logistic function and the shear strength parameters varying with wetting duration and degree of saturation. Their weathering and water-softening effects are reproduced with the use of the ABAQUS finite-element software and MATLAB programming. The proposed numerical method is applied to analyze the seepage field and stability of a highway cut slope with and without protection structures; the application results show that the proposed numerical method is reliable in analyzing the slope's instability problem. The use of the herringbone skeleton structures can reduce the water-softening effects and thus increase the safety factor of the slope. The findings of this study could provide guidance to the design and construction of highway cut slopes in mountain areas that are rich in carbonaceous mudstone.

7.
Univers Access Inf Soc ; : 1-20, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36160368

RESUMO

This study aims to investigate older adults' psychological reactions when facing changes in daily life caused by the COVID-19 pandemic and anti-epidemic measures. Specifically, this study investigated the impacts of communication types (i.e., electronic and face-to-face communication) and frequency during the pandemic and the kinds of proactive coping actions taken by older adults on their anxiety. A total of 43,019 respondents were included in this study by merging two longitudinal databases. One is the seventh wave of the Survey of Health, Ageing and Retirement in Europe (SHARE) conducted in 2017, and the other is the COVID-19 Survey of SHARE, which was conducted between June and August 2020. This study found that one third of older adults reported anxiety symptoms during the COVID-19 pandemic and one fifth reported increased anxiety than before the pandemic. Anxiety symptoms seem somewhat prevalent among older adults during the COVID-19 pandemic. During the pandemic, the more kinds of proactive coping actions taken by older adults, the more likely they felt anxious. As the pandemic continues and develops, taking proactive coping actions might no longer alleviate anxiety in older adults, showing a diminishing utility. In addition, face to face communication was found to decrease the likelihood of anxiety symptoms in older adults, whereas the opposite impact of electronic communication was found. For older adults, contacting others by electronic means may increase their anxiety feeling during the COVID-19 pandemic.

8.
J Bone Miner Metab ; 40(6): 1007-1013, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36036835

RESUMO

BACKGROUND AND AIM: Apolipoprotein D (ApoD) is a 25-30 kDa glycoprotein, as a distinct component of the human plasma lipoprotein system. Its known biological functions are mainly related to lipid metabolism. The purpose of this study was to explore the potential role of ApoD concentration in knee osteoarthritis (KOA). METHODS: This study was performed in a population of 113 KOA subjects and 97 healthy controls. Serum ApoD was detected using the commercial ELISA kit (Cusabio, Wu Han, China, Cat No. CSB-EL001935HU). Radiographic progression was evaluated using Kellgren-Lawrence (KL) classification. The clinical severity of KOA was assessed by visual analog score (VAS), Hospital for special surgery (HSS) knee score disease duration and TNF-α. Receiver-operating characteristic (ROC) curve was performed to test the potential diagnostic value of ApoD in radiographic progression. RESULTS: The serum ApoD level of patients with KOA was significantly lower than that of healthy controls. The serum ApoD level was negatively correlated with KL grades, VAS score, disease duration, TNF-α concentrations. On the contrary, it was positively correlated with HSS score. However, there was no correlation between this serological indicator and which side was affected. ROC curve analysis indicated that attenuated serum ApoD could serve as an appropriate biomarker concerning the diagnosis of KOA. CONCLUSIONS: Serum ApoD concentration was correlated with the presence and severity of KOA.


Assuntos
Osteoartrite do Joelho , Fator de Necrose Tumoral alfa , Humanos , Índice de Gravidade de Doença , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/metabolismo , Biomarcadores/metabolismo , Curva ROC
9.
Water Sci Technol ; 85(1): 116-124, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35050870

RESUMO

This study aimed to determine the effects of D-tyrosine, D-aspartic acid, D-tryptophan and D-leucine on biofilm formation of mixed microorganisms. Results showed that, in the attachment stage, D-amino acids caused significant reduction in adhesion efficiency of mixed microorganisms to the membrane surface. Moreover, D-amino acids have a promoting effect on the reversible adhesion of mixed microorganisms. The addition of D-amino acid generally inhibited the biofilm biomass, of which D-tyrosine has the best inhibition effect. With the effect of D-tyrosine, D-aspartic acid, D-tryptophan and D-leucine, the protein in extracellular polymeric substance (EPS) decreased by 8.21%, 7.65%, 3.51% and 11.31%, respectively. The carbohydrates in EPS decreased by 29.53%, 21.44%, 14.60% and 10.54%, respectively. The results of excitation-emission matrix spectra (EEMs) suggested that the structural properties of the tyrosine-like proteins, tryptophan-like protein and humic-like acid might have changed by the D-amino acids.


Assuntos
Aminoácidos , Matriz Extracelular de Substâncias Poliméricas , Biofilmes , Tirosina
10.
Curr Biol ; 31(20): 4449-4461.e4, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34437843

RESUMO

To make adaptive feeding and foraging decisions, animals must integrate diverse sensory streams with multiple dimensions of internal state. In C. elegans, foraging and dispersal behaviors are influenced by food abundance, population density, and biological sex, but the neural and genetic mechanisms that integrate these signals are poorly understood. Here, by systematically varying food abundance, we find that chronic avoidance of the population-density pheromone ascr#3 is modulated by food thickness, such that hermaphrodites avoid ascr#3 only when food is scarce. The integration of food and pheromone signals requires the conserved neuropeptide receptor PDFR-1, as pdfr-1 mutant hermaphrodites display strong ascr#3 avoidance, even when food is abundant. Conversely, increasing PDFR-1 signaling inhibits ascr#3 aversion when food is sparse, indicating that this signal encodes information about food abundance. In both wild-type and pdfr-1 hermaphrodites, chronic ascr#3 avoidance requires the ASI sensory neurons. In contrast, PDFR-1 acts in interneurons, suggesting that it modulates processing of the ascr#3 signal. Although a sex-shared mechanism mediates ascr#3 avoidance, food thickness modulates this behavior only in hermaphrodites, indicating that PDFR-1 signaling has distinct functions in the two sexes. Supporting the idea that this mechanism modulates foraging behavior, ascr#3 promotes ASI-dependent dispersal of hermaphrodites from food, an effect that is markedly enhanced when food is scarce. Together, these findings identify a neurogenetic mechanism that sex-specifically integrates population and food abundance, two important dimensions of environmental quality, to optimize foraging decisions. Further, they suggest that modulation of attention to sensory signals could be an ancient, conserved function of pdfr-1.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Feminino , Masculino , Feromônios , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais , Fatores de Transcrição
11.
G3 (Bethesda) ; 10(1): 199-210, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31690562

RESUMO

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.


Assuntos
Aprendizagem da Esquiva , Proteínas de Caenorhabditis elegans/metabolismo , Interneurônios/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Interneurônios/fisiologia , Locomoção , Mutação com Perda de Função , Proteínas do Tecido Nervoso/genética , Olfato
12.
Dev Cell ; 49(4): 542-555.e9, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-30956008

RESUMO

Biological roles for most long non-coding RNAs (lncRNAs) remain mysterious. Here, using forward genetics, we identify lep-5, a lncRNA acting in the C. elegans heterochronic (developmental timing) pathway. Loss of lep-5 delays hypodermal maturation and male tail tip morphogenesis (TTM), hallmarks of the juvenile-to-adult transition. We find that lep-5 is a ∼600 nt cytoplasmic RNA that is conserved across Caenorhabditis and possesses three essential secondary structure motifs but no essential open reading frames. lep-5 expression is temporally controlled, peaking prior to TTM onset. Like the Makorin LEP-2, lep-5 facilitates the degradation of LIN-28, a conserved miRNA regulator specifying the juvenile state. Both LIN-28 and LEP-2 associate with lep-5 in vivo, suggesting that lep-5 directly regulates LIN-28 stability and may function as an RNA scaffold. These studies identify a key biological role for a lncRNA: by regulating protein stability, it provides a temporal cue to facilitate the juvenile-to-adult transition.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/crescimento & desenvolvimento , RNA Longo não Codificante/metabolismo , Proteínas Repressoras/metabolismo , Sequência de Aminoácidos , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Morfogênese/genética , Morfogênese/fisiologia , Mutação , Fenótipo , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Fatores de Transcrição/metabolismo
13.
Curr Biol ; 28(6): 902-914.e5, 2018 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-29526590

RESUMO

Biological sex, a fundamental dimension of internal state, can modulate neural circuits to generate behavioral variation. Understanding how and why circuits are tuned by sex can provide important insights into neural and behavioral plasticity. Here we find that sexually dimorphic behavioral responses to C. elegans ascaroside sex pheromones are implemented by the functional modulation of shared chemosensory circuitry. In particular, the sexual state of a single sensory neuron pair, ADF, determines the nature of an animal's behavioral response regardless of the sex of the rest of the body. Genetic feminization of ADF causes males to be repelled by, rather than attracted to, ascarosides, whereas masculinization of ADF has the opposite effect in hermaphrodites. When ADF is ablated, both sexes are weakly repelled by ascarosides. Genetic sex modulates ADF function by tuning chemosensation: although ADF is functional in both sexes, it detects the ascaroside ascr#3 only in males, a consequence of cell-autonomous action of the master sexual regulator tra-1. This occurs in part through the conserved DM-domain gene mab-3, which promotes the male state of ADF. The sexual modulation of ADF has a key role in reproductive fitness, as feminization or ablation of ADF renders males unable to use ascarosides to locate mates. Our results reveal an economical mechanism in which sex-specific behavioral valence arises through the cell-autonomous regulation of a chemosensory switch by genetic sex, allowing a social cue with salience for both sexes to elicit navigational responses commensurate with the differing needs of each.


Assuntos
Aptidão Genética/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Comportamento Animal/fisiologia , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/fisiologia , Células Quimiorreceptoras/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , Feminino , Masculino , Sistema Nervoso , Neurônios/fisiologia , Células Receptoras Sensoriais/metabolismo , Atrativos Sexuais/metabolismo , Caracteres Sexuais , Comportamento Sexual Animal/fisiologia , Fatores de Transcrição/genética
14.
Genetics ; 199(2): 523-31, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25527285

RESUMO

Methyl salicylate (MeSa) is a stress hormone released by plants under attack by pathogens or herbivores . MeSa has been shown to attract predatory insects of herbivores and repel pests. The molecules and neurons underlying animal response to MeSa are not known. Here we found that the nematode Caenorhabditis elegans exhibits a strong avoidance response to MeSa, which requires the activities of two closely related neuropeptide receptors NPR-1 and NPR-2. Molecular analyses suggest that NPR-1 expressed in the RMG inter/motor neurons is required for MeSa avoidance. An NPR-1 ligand FLP-18 is also required. Using a rescuing npr-2 promoter to drive a GFP transgene, we identified that NPR-2 is expressed in multiple sensory and interneurons. Genetic rescue experiments suggest that NPR-2 expressed in the AIZ interneurons is required for MeSa avoidance. We also provide evidence that the AWB sensory neurons might act upstream of RMGs and AIZs to detect MeSa. Our results suggest that NPR-2 has an important role in regulating animal behavior and that NPR-1 and NPR-2 act on distinct interneurons to affect C. elegans avoidance response to MeSa.


Assuntos
Comportamento Animal/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/fisiologia , Reguladores de Crescimento de Plantas/farmacologia , Salicilatos/farmacologia , Estresse Fisiológico , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/metabolismo
15.
G3 (Bethesda) ; 5(2): 195-203, 2014 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-25480962

RESUMO

Iodine is an essential trace element for life. Iodide deficiency can lead to defective biosynthesis of thyroid hormones and is a major cause of hypothyroidism and mental retardation. Excess iodide intake, however, has been linked to different thyroidal diseases. How excess iodide causes harmful effects is not well understood. Here, we found that the nematode Caenorhabditis elegans exhibits developmental arrest and other pleiotropic defects when exposed to excess iodide. To identify the responsible genes, we performed a forward genetic screen and isolated 12 mutants that can survive in excess iodide. These mutants define at least four genes, two of which we identified as bli-3 and tsp-15. bli-3 encodes the C. elegans ortholog of the mammalian dual oxidase DUOX1 and tsp-15 encodes the tetraspanin protein TSP-15, which was previously shown to interact with BLI-3. The C. elegans dual oxidase maturation factor DOXA-1 is also required for the arresting effect of excess iodide. Finally, we detected a dramatically increased biogenesis of reactive oxygen species in animals treated with excess iodide, and this effect can be partially suppressed by bli-3 and tsp-15 mutations. We propose that the BLI-3/TSP-15/DOXA-1 dual oxidase complex is required for the toxic pleiotropic effects of excess iodide.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/efeitos dos fármacos , Iodetos/toxicidade , Oxirredutases/genética , Tetraspaninas/genética , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Mutação , Espécies Reativas de Oxigênio/metabolismo
16.
RNA Biol ; 11(9): 1148-60, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25483032

RESUMO

Spinal muscular atrophy (SMA), the most frequent human congenital motor neuron degenerative disease, is caused by loss-of-function mutations in the highly conserved survival motor neuron gene SMN1. Mutations in SMN could affect several molecular processes, among which aberrant pre-mRNA splicing caused by defective snRNP biogenesis is hypothesized as a major cause of SMA. To date little is known about the interactions of SMN with other splicing factor genes and how SMN affects splicing in vivo. The nematode Caenorhabditis elegans carries a single ortholog of SMN, smn-1, and has been used as a model for studying the molecular functions of SMN. We analyzed RNA splicing of reporter genes in an smn-1 deletion mutant and found that smn-1 is required for efficient splicing at weak 3' splice sites. Genetic studies indicate that the defective lifespan and motor functions of the smn-1 deletion mutants could be significantly improved by mutations of the splicing factor U2AF large subunit gene uaf-1. In smn-1 mutants we detected a reduced expression of U1 and U5 snRNAs and an increased expression of U2, U4 and U6 snRNAs. Our study verifies an essential role of smn-1 for RNA splicing in vivo, identifies the uaf-1 gene as a potential genetic modifier of smn-1 mutants, and suggests that SMN-1 has multifaceted effects on the expression of spliceosomal snRNAs.


Assuntos
Envelhecimento/genética , Animais Geneticamente Modificados/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Neurônios Motores/fisiologia , Proteínas Nucleares/metabolismo , Ribonucleoproteínas/metabolismo , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/crescimento & desenvolvimento , Comportamento Animal , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/genética , Humanos , Mutação/genética , Proteínas Nucleares/genética , Precursores de RNA/genética , Precursores de RNA/metabolismo , Splicing de RNA , Ribonucleoproteínas/genética , Ribonucleoproteínas Nucleares Pequenas/genética , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Fator de Processamento U2AF , Proteína 1 de Sobrevivência do Neurônio Motor/genética
17.
PLoS Genet ; 8(7): e1002827, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22829783

RESUMO

RNA splicing is a major regulatory mechanism for controlling eukaryotic gene expression. By generating various splice isoforms from a single pre-mRNA, alternative splicing plays a key role in promoting the evolving complexity of metazoans. Numerous splicing factors have been identified. However, the in vivo functions of many splicing factors remain to be understood. In vivo studies are essential for understanding the molecular mechanisms of RNA splicing and the biology of numerous RNA splicing-related diseases. We previously isolated a Caenorhabditis elegans mutant defective in an essential gene from a genetic screen for suppressors of the rubberband Unc phenotype of unc-93(e1500) animals. This mutant contains missense mutations in two adjacent codons of the C. elegans microfibrillar-associated protein 1 gene mfap-1. mfap-1(n4564 n5214) suppresses the Unc phenotypes of different rubberband Unc mutants in a pattern similar to that of mutations in the splicing factor genes uaf-1 (the C. elegans U2AF large subunit gene) and sfa-1 (the C. elegans SF1/BBP gene). We used the endogenous gene tos-1 as a reporter for splicing and detected increased intron 1 retention and exon 3 skipping of tos-1 transcripts in mfap-1(n4564 n5214) animals. Using a yeast two-hybrid screen, we isolated splicing factors as potential MFAP-1 interactors. Our studies indicate that C. elegans mfap-1 encodes a splicing factor that can affect alternative splicing.


Assuntos
Processamento Alternativo/genética , Caenorhabditis elegans/genética , Proteínas Contráteis/genética , Proteínas da Matriz Extracelular/genética , Precursores de RNA/genética , Sítios de Splice de RNA/genética , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Proteínas de Caenorhabditis elegans/genética , Éxons/genética , Expressão Gênica , Íntrons/genética , Proteínas de Membrana/genética , Dados de Sequência Molecular , Mutação de Sentido Incorreto/genética , Proteínas Nucleares/genética , Fenótipo , Isoformas de Proteínas , Fatores de Processamento de RNA , Ribonucleoproteínas/genética , Homologia de Sequência de Aminoácidos
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