MOLECULAR NEUROBIOLOGY
·
2024
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IF 4.6
Shen Yifen,Zhang Le,Yang Tao,Li Xiaosong,Liu Chao,Li Hongmei,Hu Yanping,Shen Hao,Li Hua,Orlov Yuriy L.,Zhou Shasha,Shen Yihang
Puberty onset through hypothalamic-pituitary-gonad (HPG) axis as an important reproductive event in postnatal development is initiated from hypothalamic arcuate nucleus (ARC). The growing evidence indicates that translational control also plays an essential role in the final expression of gonadotropin genes. To investigate the role of protein translation and behavior of ribosomes in pubertal onset, the global profiles of transcriptome, single ribosome (monosome), polysome, and tandem mass tag proteome were comprehensively investigated in rat hypothalamic ARCs of different pubertal stages using RNA sequencing, polyribo sequencing, and mass spectrum. Transcriptome-wide enrichments of N6-methyladenosine and IGF2BP2 were investigated using meRIP and RIP sequencing. Monosome was robustly enriched on a large proportion of mRNA in early puberty rats (postnatal day (PND)-25) compared to late puberty (PND-35 and PND-45). Monosome-enriched mRNAs, including HPG axis-related genes, had a large number of upstream ORFs (uORF, < 100 nt) and displayed translational repression in early puberty. Furthermore, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could particularly interact with and facilitate monosome to bind with mRNA in early puberty. Finally, ectopic over-expression of IGF2BP2 in hypothalamic ARC via lateral ventricle injection in vivo could recruit monosome to aggregate on mRNA and delay puberty onset. We uncovered a novel regulatory mechanism of IGF2BP2 and monosome for translational control in puberty onset, which shed light on the neuroendocrine regulatory network involved in HPG axis activation.
研究领域:
神经内分泌学
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生殖生物学
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翻译调控
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2016
·Vol. 11
·期 10
·e0163340
·
IF 3.057
Hong Zhou,Yapei Wang,Qiongying Lv,Juan Zhang,Qing Wang,Fei Gao,Haoli Hou,Hao Zhang,Wei Zhang,Lijia Li
The ribosomal RNA (rRNA) gene encodes rRNA for protein synthesis. Aberrant expression of the rRNA gene has been generally observed in tumor cells and levels of its promoter methylation as an epigenetic regulator affect rRNA gene transcription. The possible relationship between expression and promoter methylation of rDNA has not been examined in human clinical cervical cancer. Here we investigate rRNA gene expression by quantitative real time PCR, and promoter methylation levels by HpaII/MspI digestion and sodium bisulfite sequencing in the development of human cervical cancer. We find that indeed rRNA levels are elevated in most of cervical intraepithelial neoplasia (CIN) specimens as compared with non-cancer tissues. The rDNA promoter region in cervical intraepithelial neoplasia (CIN) tissues reveals significant hypomethylation at cytosines in the context of CpG dinucleotides, accompanied with rDNA chromatin decondensation. Furthermore treatment of HeLa cells with the methylation inhibitor drug 5-aza-2’-deoxycytidine (DAC) demonstrates the negative correlation between the expression of 45S rDNA and the methylation level in the rDNA promoter region. These data suggest that a decrease in rDNA promoter methylation levels can result in an increase of rRNA synthesis in the development of human cervical cancer.
研究领域:
分子生物学
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肿瘤学
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表观遗传学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
·
2021
·
IF 4.155
Kun Chen,Qiang Yu,Yuan Liu,Panchao Yin
Developing strategies against the antibiotic resistance is a major global challenge for public health. Here, we report the synergy of the combination of Preyssler-type polyoxometalates (POMs) ([NaP 5 W 30 O 110 ] 14− or [AgP 5 W 30 O 110 ] 14− ) and ribosome-targeting antibiotics for high antibacterial efficiency with low risk of antibiotic resistance. Due to their ultra-small sizes and active surface ligands, POM anions show strong affinity to bacterial cell membrane and impose hyperpolarization of the bacterial cells as well as the decrease of Mg 2+ influx by blocking Mg 2+ transporters, which finally lead to the structural perturbations of ribosomes and instability of bacterial structures. The bacterial growth can, therefore, be regulated by the presence of POMs: a fraction of Bacillus subtilis shifted to a ‘dormant’, slow-growing cellular state (an extended lag phase) upon the application of subinhibitory concentration of POMs. An approach to combat antibiotic resistant bacteria by applying POMs at their early growth phase followed by antibiotic exposure is validated, and its high efficiency for bacterial control is confirmed.
研究领域:
微生物学
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药学
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生物技术
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材料科学
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产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2017
·Vol. 8
·期 8
·13240
·
IF 5.168
Zhixiong Dong,Changjun Zhu,Qimin Zhan,Wei Jiang
The nucleolus controls ribosome biogenesis and its perturbation induces nucleolar stress that inhibits cell cycle progression and activates checkpoint responses. Here, we investigate the roles of ribosomal RNA processing protein, RRP15, in nucleolar formation, ribosome biogenesis, cell cycle progression and checkpoint control in human cells. RRP15 is localized in the nucleolus and required for nucleolar formation. In contrast to the budding yeast Rrp15p that was reported as a component of pre-60S subunits, RRP15 is found in both pre-40S and pre-60S subunits and involved in regulating rRNA transcription and ribosome biogenesis. Perturbation of RRP15 induces nucleolar stress that activates RPL5/RPL11/5S rRNA (RP)-Mdm2-p53 axis checkpoint response and arrests cells at G1-G1/S in p53-proficient non-transformed RPE1 cells but not in p53-deficient HeLa and MCF7 tumor cells. Instead, p53-deficient HeLa and MCF7 cells with RRP15-dependent nucleolar stress enter S-phase with S-phase perturbation that activates ATR-Chk1- γH2AX axis DNA replication/damage checkpoint response, delaying S-G2/M progression and, ultimately, causing cell death. The selective checkpoint response, cell cycle inhibition and/or cytotoxicity induced by RRP15-dependent nucleolar stress in p53-proficient non-transformed cells and p53-deficient tumor cells suggest that RRP15 might be a potential target for cancer therapy.
研究领域:
分子生物学
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细胞生物学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
ACS Chemical Biology
·
2020
·
IF 4.434
Feifei Luo,Song Hong,Bo Chen,Ying Yin,Guirong Tang,Fenglin Hu,Huizhan Zhang,Chengshu Wang
The indolizidine alkaloid swainsonine (SW) is a deadly mycotoxin to livestock that can be produced by different plant-associated fungi, including the endophytic entomopathogenic fungi Metarhizium species. The SW biosynthetic gene cluster has been identified but the genetic mechanism of SW biosynthesis remains obscure. To unveil the SW biosynthetic pathway, we performed gene deletions in M. robertsii, heterologous expression of a core biosynthetic gene, substrate feedings, mass spectrometry, and bioassay analyses in this study. It was unveiled that SW is produced via a multibranched pathway by the hybrid nonribosomal peptide–polyketide synthase (NRPS-PKS) gene cluster in M. robertsii. The precursor pipecolic acid can be converted from lysine by both the SW biosynthetic cluster and the unclustered genes such as lysine cyclodeaminase. The hybrid NRPS-PKS enzyme produces three intermediates with and without domain skipping. Intriguingly, the biosynthetic process is coupled with the cis to trans nonenzymatic epimerization of C1-OH for both hydroxyl- and dihydroxyl-indolizidine intermediates. We also found that SW production was dispensable for fungal colonization of plants and infection of insect hosts. Functional characterization of the SW biosynthetic genes in this study may benefit the safe use of Metarhizium fungi as insect biocontrol agents and the management of livestock pastures from SW contamination by genetic manipulation of the toxin-producing fungi.
研究领域:
微生物学
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分子生物学
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遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Fermentation-Basel
·
2023
·Vol. 9
·期 4
·398
·
IF 3.7
Hongyu Zhang,Deguang Zhang,Ran Liu,Tingting Lou,Ruyue Tan,Suying Wang
The special structure of pentostatin causes it to possess a wide spectrum of biological and pharmacological properties, and it has been extensively employed to treat malignant tumors and is the first-line treatment for hairy cell leukemia. Pentostatin is mainly distributed in several actinomycetes and fungi species. However, its low titer in microbes is not able to meet medical needs. Here, we report a strain improvement strategy based on combined atmospheric and room-temperature plasma (ARTP) mutagenesis and ribosome engineering screening, as well as fermentation optimization, for enhanced pentostatin production. The original strain,Actinomadurasp. ATCC 39365, was treated with ARTP and screened by ribosome engineering to obtain one stable pentostatin high-yield mutantActinomadurasp. S-15, which produced 86.35 mg/L pentostatin, representing a 33.79% increase compared toActinomadurasp. ATCC 39365. qRT-PCR analysis revealed that pentostatin biosynthesis-related gene expression was significantly upregulated inActinomadurasp. S-15. Then, to further enhance pentostatin production, the fermentation medium was optimized in flask culture and the pentostatin production ofActinomadurasp. S-15 reached 152.06 mg/L, which is the highest pentostatin production reported so far. These results demonstrate the effectiveness of combined ARTP mutation, ribosome engineering screening, and medium optimization for the enhancement of pentostatin production, and provide a methodology enabling the sustainable production of pentostatin on an industrial scale.Keywords:Actinomadurasp.;pentostatin;atmospheric and room temperature plasma;ribosome engineering
研究领域:
微生物学
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生物技术
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药理学
✓ 已验证
产品关联
DOI
高影响因子
ENVIRONMENTAL POLLUTION
·
2021
·
IF 8.071
Minfen Gu,WenWen Fang,Xiaoning Li,Weiben Yang,Michael Gatheru Waigi,Fredrick Orori Kengara,Shixi Wu,Cheng Han,Yinping Zhang
The polycyclic aromatic hydrocarbons (PAHs) that enter the aqueous phase usually coexist with fulvic acid (FA). Therefore, we initiated this investigation to explore the influences of FA on bacterial biofilm formation and its potential to biodegrade pyrene (PYR), using electron microscopic techniques and isobaric tags for relative and absolute quantification (iTRAQ). Our results revealed that FA stimulated biofilm formation and enhanced the biodegradation of PYR. First, FA favored the three-dimensional proliferation of bacteria, with an OD590/OD600 value of up to 14.78, and the extracellular surfaces covered by a layer of biomaterials. Distinctive intracellular morphologies of texture and organization were accompanied by reduced inter-bacterial distances of less than 0.31 μm. The biofilms formed displayed interactions between FA and surficial proteins, as noted by band shifts for the C–O and C O groups. Strikingly, FA triggered the upregulation of 130 proteins that were either operational in biofilm formation or in metabolic adjustments; with the changes supported by the increasing intensity of free amino acids and the newly generated N–O bonds. The results above revealed that the enhanced biodegradation was related to the up-regulation of the proteins functioned for ribosomal and carbon metabolism, and the ultra-structural changes in FA-induced biofilm system.
研究领域:
环境科学
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微生物学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2022
·
IF 3.322
Zixin Li,Luchen Shan,Pei Yu
Nitroglycerin (NTG) is recommended as the first-line drug in angina pectoris though its prolonged use impacts nitroglycerin tolerance. In this study, we investigated the preventive effect of Tetramethylpyrazine (TMP), a famous Chinese medicine used for cardiovascular diseases, on NTG-induced tolerance and further explained the underlying mechanism of its action. The results revealed that pretreatment of TMP improved NTG-induced tolerance in vitro thoracic aorta rings and in rats. Proteomic analysis showed oxidative stress and ribosome proteins dyshomeostasis in NTG-tolerance vessels. TMP attenuated the oxidative stress by enhancing the protein expression of ALDH2 , Nrf2 and HO-1. In addition, TMP recovered the down-regulated expression of RpL10a induced by nitroglycerin. Therefore, TMP could prevent nitroglycerin tolerance in rats, which may be mediated by up-regulation of ALDH2 and Nrf2/HO-1 signaling pathway and involved in the restoration of ribosome homeostasis . These findings indicate the potential of TMP as a promising medicine for preventing the development of nitroglycerin-induced tolerance.
研究领域:
心血管药理学
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分子生物学
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药物动力学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Hang-fei Chen,Zhang-ping Li,Qi Wu,Chun Yu,Jing-Yi Yan,Yong-feng Bai,Sheng-mei Zhu,Mao-xiang Qian,Ming Liu,Li-feng Xu,Zheng Peng,Feng Zhang
Hyperactivation of ribosome biosynthesis (RiBi) is a hallmark of cancer, and targeting ribosome biogenesis has emerged as a potential therapeutic strategy. The depletion of TAF1B , a major component of selectivity factor 1 ( SL1 ), disrupts the pre-initiation complex, preventing RNA polymerase I from binding ribosomal DNA and inhibiting the hyperactivation of RiBi. Here, we investigate the role of TAF1B , in regulating RiBi and proliferation in stomach adenocarcinoma (STAD). We disclosed that the overexpression of TAF1B correlates with poor prognosis in STAD, and found that knocking down TAF1B effectively inhibits STAD cell proliferation and survival in vitro and in vivo. TAF1B knockdown may also induce nucleolar stress, and promote c-MYC degradation in STAD cells. Furthermore, we demonstrate that TAF1B depletion impairs rRNA gene transcription and processing, leading to reduced ribosome biogenesis. Collectively, our findings suggest that TAF1B may serve as a potential therapeutic target for STAD and highlight the importance of RiBi in cancer progression.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CARBON
·
2024
·
IF 10.5
Yuting Liu,Chao Huang,Wenhui Yue,Xiaoning Wang,Yiping Sun,Weilin Bi,Lu Wang,Yuanhong Xu
With the gradual development of carbon dots (CDs) in the antimicrobic application, efforts have been still devoted to overcome the dilemma that more effective antibacterial treatment would lead to inevitable higher cytotoxicity. In addition, their bactericidal mechanisms are still in urgent need to be clarified. Therefore, silver (copper)-containing carbon dots have been prepared via one microwave-irradiation strategy using glucose as precursors and metal salts as passivators. It was discovered that the as-prepared metal-containing CDs have the comparable or better bactericidal effect while lower cytotoxicity towards mammalian cells compared with most of corresponding commercial metal-containing antibacterial agents and their free metal ions, because of the good permeability towards bacterial cells originating from the excellent metal dispersion and glucose disguiser in/on the CDs. The minimum bactericidal concentration of silver(copper)-containing carbon dots against 1.5 (0.5) × 10 7 CFU/mL Escherichia coli was less than 25 (75) μg/mL. Different bactericidal mechanisms between the two metal-containing CDs and the free copper/silver ions were revealed in details. It was found that the metal ions could directly inhibit the function of ribosomes in bacterial cells, while the metal-containing CDs showed negligible influence towards ribosome directly, instead, they inhibited bacterial metabolism through more complex pathways such as metabolic disorders, transporter inactivation or inhibition of the nucleic acid synthesis. Since the mammalians cells can switch to other pathways more flexibly than bacterial cells under the disturbance of the same metabolism pathway inhibition, the metal-containing CDs provides excellent biocompatibility.
研究领域:
材料科学
·
纳米技术
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生物医学工程
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微生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF APPLIED MICROBIOLOGY
·
2021
·Vol. 131
·期 2
·791-800
·
IF 3.772
Hou W.,Zhang Y.,Zhang Y.,Yue Q.,Wang L.,Min T.,Wang H.
AimsThe purpose of this study was to investigate the regulatory mechanism of ε‐PL on Shewanella putrefaciens.Methods and ResultsProteomics analysis of inhibitory effect of ε‐PL against S. putrefaciens was performed by label‐free quantitative assay based on high‐resolution mass spectrometry (MS). Quantification of 2206 proteins was obtained with high confidence, and a total of 36 differentially expressed proteins (DEPs), with 10 and 26 proteins showing upregulation and downregulation, respectively, were identified. Upon Go functional enrichment, 11, 5 and 8 specific Go terms in biological processes, molecular functions and cellular components were identified, respectively. Six KEGG pathways, including ‘ribosome’, were significantly enriched. Among the ribosome pathway, there were seven DEPs and all of them were distributed on large and small subunits of ribosome.ConclusionsThe significant downregulation of proteins, large subunits of ribosomal proteins RP‐L18, L30 and L27, small subunits ribosomal proteins S16 and S20, and RNA polymerase β' subunit protein rpoC were the critical action sites of ε‐PL to inhibit S. putrefaciens growth.Significance and Impact of the StudyShewanella putrefaciens is one of the representative fish‐spoilage bacteria regardless of fish type, and poses significant problems for the fish brewery. A better understanding of the antibacterial mechanism of ε‐PL on S. putrefaciens could make important contributions to development of biological control strategies of these economically important pathogens.
研究领域:
微生物学
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蛋白质组学
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食品科学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Su Jiyan,Chen Xiaohong,Xiao Yuanjie,Li Dan,Li Muxia,Li Hongfu,Huang Jiangjian,Lai Zhengquan,Su Ziren,Xie Yizhen,Zhu Dajiang,Chen Qianjun,Lu Hai,He Jingjin,Xia Chenglai
Triple-negative breast cancer (TNBC) has been acknowledged as an aggressive disease with worst prognosis, which requires endeavor to develop novel therapeutic agents. Bruceae fructus oil (BO), a vegetable oil derived from the fruit of Brucea javanica (L.) Merr., is an approved marketable drug for the treatment of cancer in China for several decades. Despite that the anti–breast cancer activity of several quassinoids derived from B. javanica has been found, it was the first time that the potential of BO against TNBC was revealed. Although BO had no cytotoxicity on TNBC cell lines in vitro, the oral administration of BO exhibited a gut microbiota–dependent tumor suppression without toxicity on the non-targeted organs in vivo. By metagenomics and untargeted metabolomics, it was found that BO not only altered the composition and amino acid metabolism function of gut microbiota but also regulated the host’s amino acid profile, which was in accordance with the metabolism alternation in gut microbiota. Moreover, the activity of mTOR in tumor was promoted by BO treatment as indicated by the phosphorylation of 4E-binding protein 1 (4E-BP1) and ribosomal protein S6, and hyper-autophagy was consequently restrained. By contrast, the failure of tumor suppression by BO under pseudo germ-free (PGF) condition came with indistinctive changes in autophagy and mTOR activity, implying the critical role of the gut microbiota in BO’s anticancer activity. The present study highlighted a promising application of BO against breast cancer with novel efficacy and safety.
研究领域:
肿瘤学
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药理学
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微生物学
·
代谢组学
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癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）