INFECTION GENETICS AND EVOLUTION
·
2021
·
IF 3.342
Congshan Liu,Jianping Cao,Haobing Zhang,Jianhai Yin
RNA modifications, as one of epigenetic mechanisms, are important and conserved mechanisms for maintaining the homeostasis of organisms. Little is known about RNA modifications in Echinococcus granulosus, an obligate parasite that inhabits mammals and gives rise to a huge public health and economic impact. Here, we focused on the RNA modification characteristics of E. granulosus for the first time by using mass spectrometry (UPLC-MS/MS) to qualitatively and quantitatively analyze 47 types of RNA modifications in E. granulosus total RNA. Furthermore, the E. granulosus homologs of writer enzymes preforming RNA modifications were identified, and their gene expression pattern at different developmental stages were analyzed by bioinformatics analysis. Finally, 23 types of RNA modifications were found in E. granulosus cysts total RNA, of which m 1 A, Ψ and m 5 C are the most abundant. The homologs of writer enzymes involved in these modifications were identified in the E. granulosus genome, with the dynamic gene expression during the different parasitic developmental stages. This work confirms that E. granulosus retains the conserved RNA modification mechanism during evolution, suggesting the important role of RNA modification in regulating its development and parasitic process. Moreover, the differences of amino acid sequences of RNA modification writer enzymes between parasite and host make it possible to use these enzymes as the candidate drug targets in the follow-up in-depth researches.
研究领域:
寄生虫学
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分子生物学
·
基因组学
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DOI
PubMed
高影响因子
Virulence
·
2025
·
IF 5.4
Zijing Liang,Shuoyue Wang,Xinchi Zhu,Jiale Ma,Huochun Yao,Zongfu Wu
Streptococcus suis is a Gram-positive pathogen causing septicaemia and meningitis in pigs and humans. However, how S. suis maintains a high bacterial load in the blood and brain is poorly understood. In this study, we found that a small RNA rss03 is predominantly present in S. suis, Streptococcus parasuis, and Streptococcus ruminantium, implying a conserved biological function. rss03 with a size of 303 nt mainly exists in S. suis sequence type (ST) 1 and epidemic ST7 strains that are responsible for human infections in China. Using MS2-affinity purification coupled with RNA sequencing (MAPS), proteomics analysis, and CopraRNA prediction, 14 direct targets of rss03 from an ST7 strain were identified. These direct targets mainly involve substance transport, transcriptional regulation, rRNA modification, and stress response. A more detailed analysis reveals that rss03 interacts with the coding region of glpF mRNA, and unexpectedly rss03 protects glpF mRNA from degradation by RNase J1. The GlpF protein is an aquaporin, contributes to S. suis oxidative stress resistance by H2O2 efflux, and facilitates bacterial survival in murine macrophages RAW264.7. Finally, we showed that rss03 and GlpF are required to maintain a high bacterial load in mouse blood and brain. Our study presents the first sRNA targetome in streptococci, enriches the knowledge of sRNA regulation in streptococci, and identifies pathways contributing to S. suis pathogenesis.
研究领域:
微生物学
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分子生物学
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感染病学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Yingwei Liu,Yunpeng Sun,Ting Zhou,Xiao Huang,Guokai Wang,Lijuan Sun
Swietenia macrophylla King, a medicine food homology, has garnered attention for the hypoglycemic and hypolipidemic activities of its fruit in the improvement of metabolic dysfunction-associated steatotic liver disease (MASLD), yet the glucolipid regulating properties of its leaf remains unexplored. The study sought to examine the pharmacological mechanisms underlying the lipid-lowering effects of Swietenia macrophylla King leaf extract (SLE) and its active constituent senegalension B (one of 31 limonoids in SLE). Glucolipid regulation by SLE and active constituent was evaluated through cellular triglyceride content and peripheral glucose levels in primary mouse hepatocytes (PMHs), SLE dose-dependently reduced lipid accumulation in the range of 23.65±3.41% to 37.39±2.50%, validated by Oil Red O staining. Network pharmacology and RNA sequencing identified SREBP-1c/FASN axis as the key mechanism by which SLE improved lipid accumulation in PMHs, consistent with senegalension B. RT-qPCR and Western blot showed that SLE (40 μg/mL) decreased the lipid synthesis regulator SREBP-1c mRNA and protein levels by 60.69±1.69% and 48.07±11.83%, respectively, whereas senegalension B (40 μM) achieved 55.42 ±2.29% and 34.34±8.49% inhibition. Dual-luciferase reporter assays revealed that senegalension B suppressed SREBP-1c promoter activity in Hep G2 cells. Molecular docking suggested a potential interaction with SREBP1, consistent with molecular dynamics simulation comparing binding affinity and stability with LXRα, indicating that senegalension B may exert lipid-lowering activity by targeting key proteins involved in lipid synthesis, such as SREBP-1c. This study elucidated the mechanisms and potential of SLE and senegalension B in regulating MASLD through in vitro investigation, expanded the utilization of Swietenia macrophylla King resources, and provided a candidate plant-derived compound for dietary therapy.
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产品关联
DOI
高影响因子
Genes
·
2023
·Vol. 14
·期 6
·1287
·
IF 3.5
Meng Chu,Yichao Qin,Xiuying Lin,Li Ma,Dehai Deng,Daizhu Lv,Pengcheng Fu,Huan Lin
The coconut (Cocos nuciferaL.) is a commercial crop widely distributed among coastal tropical regions. It provides millions of farmers with food, fuel, cosmetics, folk medicine, and building materials. Among these, oil and palm sugar are representative extracts. However, this unique living species ofCocoshas only been preliminarily studied at molecular levels. Benefiting from the genomic sequence data published in 2017 and 2021, we investigated the transfer RNA (tRNA) modifications and modifying enzymes of the coconut in this survey. An extraction method for the tRNA pool from coconut flesh was built. In total, 33 species of modified nucleosides and 66 homologous genes of modifying enzymes were confirmed using a nucleoside analysis using high-performance liquid chromatography combined with high-resolution mass spectrometry (HPLC-HRMS) and homologous protein sequence alignment. The positions of tRNA modifications, including pseudouridines, were preliminarily mapped using a oligonucleotide analysis, and the features of their modifying enzymes were summarized. Interestingly, we found that the gene encoding the modifying enzyme of 2′-O-ribosyladenosine at the 64th position of tRNA (Ar(p)64) was uniquely overexpressed under high-salinity stress. In contrast, most other tRNA-modifying enzymes were downregulated with mining transcriptomic sequencing data. According to previous physiological studies of Ar(p)64, the coconut appears to enhance the quality control of the translation process when subjected to high-salinity stress. We hope this survey can help advance research on tRNA modification and scientific studies of the coconut, as well as thinking of the safety and nutritional value of naturally modified nucleosides.Keywords:Cocos nucifera;epitranscriptomics;LC-MS/MS;nucleoside misidentification;RNA modification
研究领域:
植物学
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遗传学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Toxicology Research
·
2021
·Vol. 10
·期 5
·1013-1021
·
IF 3.524
Liu Yan-ping,Cai Ying,Lei Yuan-di,Yuan Xiao-yan,Wang Ye,Yi Shan,Li Xun-ya,Huang Lian,Long Ding-xin,Zhang Zhao-hui
Circular RNAs (circRNAs), is a novel type of endogenous non-coding RNAs (ncRNAs) participated in the pathogenesis of many diseases. Beryllium is one of the carcinogenesis elements. However, the mechanism and function of circRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4) was rarely reported. Therefore, the high-throughput RNA sequencing analysis was performed to detect the circRNA profiles between control groups and BeSO4-induced groups. Furthermore, circRNA-miRNA-mRNA network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and PPI network analysis were used for bioinformatics analysis. CircRNA sequencing analysis revealed that 36 circRNAs were up-regulated and 35 circRNAs were down-regulated in the BeSO4-exposed groups. The selected circRNAs were verified by real-time fluorescent quantitative PCR (qRT-PCR). Hsa_circ_0004214 and hsa_circ_0003586 were validated to be up-regulated, hsa_circ_0047958, hsa_circ_0001944, and hsa_circ_0008982 were down-regulated. The circRNA-miRNA-mRNA network annotated the key signaling pathway including cellular senescence, TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway, and Hippo signaling pathway. The PPI network indicated the most circRNAs might participate in the BeSO4 toxicity by acting as a sponge for the miR-663b through JAK–STAT signaling pathway. In summary, our study suggests that circRNAs may play roles in the mechanism of beryllium toxicity.
研究领域:
分子生物学
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毒理学
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生物信息学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2022
·
IF 5.122
Zhaomin Wang,Congcong Wang,Tianhe Fang,Yong Liu
Ribonucleic acid (RNA), a biomolecular compound polymerized by many riboside monomers as one of the most essential substances in life. Monitoring RNA changes within organisms will play an important role in the diagnosis and treatment of major genetically-related diseases. Herein, we synthesized a novel compound QOT-NA as the first example of near-infrared RNA probe with large Stokes shift . It is firstly found that the RNA probe QOT-NA has a large Stokes shift in water and buffer solvents (183–199 nm). When the probe was combined with RNA in buffer solvent, a strong emission peak appeared at about 660 nm and the fluorescence intensity increased 24 times. The imaging experiment showed that the probe QOT-NA could image RNA in cancer cells. In addition, the RNA probe QOT-NA has excellent selectivity, good sensitivity and tolerably good stability. There are good reasons to believe that the probe QOT-NA can be used as a robust RNA detection tool in the study of biological samples. Furthermore, the response principles of the probe to RNA were comprehensively discussed, including structure features, TICT mechanism and intercalative binding.
研究领域:
生物化学
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分子生物学
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医学诊断
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产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2017
·
IF 5.401
Liang Qi,Yao-Yao Fan,He Wei,Dan Zhang,Zhi-Qi Zhang
Proflavine could recognise HIV RRE (Rev response element) RNA, thus inhibiting its interaction with Rev peptide. Owing to the non-significant difference in fluorescence polarization (FP) signal between the proflavine and proflavine-RRE complex, it is not practicable for the identification of antagonists of HIV Rev peptide using proflavine as a FP probe. In the present study, graphene oxide (GO) was introduced to amplify the FP signal to enhance the sensitivity for the identification of Rev antagonists, thereby enabling the development of a primary GO-enhanced FP biosensor for the discovery of Rev antagonists. The effect of the amount of GO on the FP changes was investigated via displacement assay using a known Rev antagonist, neomycin B. The mechanism underlying the changes in FP caused by the addition of neomycin B was explored in the presence of GO. Finally, the performance of this biosensor was further evaluated using other 4 test drugs. The introduction of GO to this interaction system increased the practicability for the discovery of Rev antagonists using proflavine as a probe, and this label-free method does not suffer from limitations caused by fluorescent covalent labeling, thus providing a novel strategy for the characterization of ligand-RNA binding interactions.
研究领域:
生物物理
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分子生物学
·
药物发现
·
纳米技术
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产品关联
DOI
高影响因子
Nature Protocols
·
2022
·Vol. 17
·期 9
·1980-2007
·
IF 17.021
Liu Yusheng,Zhang Yiwei,Wang Jiaqiang,Lu Falong
Poly(A) tails are added to the 3′ ends of most mRNAs in a non-templated manner and play essential roles in post-transcriptional regulation, including mRNA export, stability and translation. Measuring poly(A) tails is critical for understanding their regulatory roles in almost every aspect of biological and medical studies. Previous methods for analyzing poly(A) tails require large amounts of input RNA (microgram-level total RNA), which limits their application. We recently developed a poly(A) inclusive full-length RNA isoform-sequencing method (PAIso-seq) at single-oocyte-level sensitivity (a single mammalian oocyte contains ~0.5 ng of total RNA) based on PacBio sequencing that enabled accurate measurement of the poly(A) tail length and non-A residues within the body of poly(A) tails along with the full-length cDNA, providing the opportunity to study precious in vivo samples with very limited input material. Here, we describe a detailed protocol for PAIso-seq library preparation from single mouse oocytes or bulk oocyte samples. In addition, we provide a complete bioinformatic pipeline to perform the analysis from the raw data to downstream analysis. The minimum time required is ~14.5 h for PAIso-seq double-stranded cDNA preparation, 2 d for PacBio sequencing in HiFi mode and 8 h for the initial data analysis.
研究领域:
分子生物学
·
基因组学
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转录组学
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DOI
PubMed
高影响因子
Science China-Chemistry
·
2025
·
IF 9.7
Chen Qianqian,Xu Haoxing,Zhao Bingyue,Patehebieke Yeersen,Zhao Zerun,Wang Xiao
The selective nucleoside synthesis through direct condensation between nucleobase and unactivated sugar in aqueous media has long been a formidable obstacle for the early chemical transformations hypothesized to construct the RNA World, due to product complexity and the low selectivity of the desired isomer. The preference of β-furanoside, the extant RNA component, has never been documented. Here we report an aqueous ribosylation mediated by divalent transition-metal ions, which unprecedentedly enhances the selectivity of furanosyl ribonucleosides as opposed to the traditionally predominating pyranosyl ones, with the furanoside/pyranoside ratio reaching up to 9/1. Furthermore, β-furanoside stands out for the first time as the most prevalent isomer in the presence of zinc and ammonium salts. The mechanism of this selectivity is elucidated with density functional theory calculations. The selectivity for β-furanoside can be further elevated via the adsorption on a zinc mineral. These findings exhibit as the first example that the selection of nucleosides with the desired, canonical configuration might be completed in the early stage of the RNA-forming process as opposed to later evolution, promoted by simple and widespread transition-metal minerals. The study may also find its value in synthetic chemistry as a guideline for developing a sustainable and selective glycosylation process.
研究领域:
生物化学
·
起源化学
·
理论生物学
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产品关联
DOI
高影响因子
Bioengineered
·
2022
·
IF 6.832
Zhipeng Jiang,Zehui Hou,Wei Liu,Zhuomin Yu,Zhiqiang Liang,Shuang Chen
The dysregulated circular RNAs (circRNAs) are linked to progression and chemoresistance in colorectal cancer (CRC). However, the role of circRNA protein tyrosine kinase 2 (circPTK2) in CRC progression and chemoresistance is uncertain. The circPTK2, microRNA (miR)-136-5p, m6A ‘reader’ protein YTH domain family protein 1 (YTHDF1), β-catenin and cyclin D1 abundances were examined via quantitative reverse transcription PCR or Western blotting. The progression was investigated by cell counting kit-8 (CCK-8), colony formation, transwell and xenograft analysis. The resistance to 5-fluorouracil (5-FU) and oxaliplatin was analyzed via detecting cell viability and apoptosis using CCK-8 analysis and flow cytometry. The binding relationship was examined through dual-luciferase reporter, RNA immunoprecipitation and pull-down analysis. In our study, circPTK2 abundance was enhanced in CRC and associated with liver metastasis, clinical stage and chemoresistance. CircPTK2 knockdown constrained cell proliferation, migration, invasion, resistance to 5-FU and oxaliplatin, and the Wnt/β-catenin signaling. MiR-136-5p was bound with circPTK2 and downregulated in CRC. MiR-136-5p knockdown attenuated the influence of circPTK2 silence on CRC progression and chemoresistance. YTHDF1 was targeted via miR-136-5p and upregulated in CRC samples and cells. MiR-136-5p targeted YTHDF1 to restrain CRC progression and chemoresistance. In addition, we confirmed that circPTK2 silence reduced xenograft tumor growth. In conclusion, circPTK2 interference suppressed CRC proliferation, migration, invasion and chemoresistance via regulating miR-136-5p and YTHDF1.Abbreviations: circRNAs: circular RNAs; CRC: colorectal cancer; circPTK2: circRNA protein tyrosine kinase 2; miR: microRNA; YTHDF1: YTH domain family protein 1; CCK-8: cell counting kit-8; 5-FU: 5-fluorouracil; RIP: RNA immunoprecipitation.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Huimin Xu,Jianqiao Chang,Hao Wu,Haoyu Wang,Wenjing Xie,Yunchao Li,Xiaohong Li,Yang Zhang,Louzhen Fan
Small interfering RNA (siRNA)-based gene therapy represents a promising strategy for tumor treatment. Novel gene vectors that can achieve targeted delivery of siRNA to the tumor cells without causing any side effects are urgently needed. To this end, the large amino acid mimicking carbon dots with guanidinium functionalization (LAAM GUA-CDs) are designed and synthesized by choosing arginine and dopamine hydrochloride as precursors. LAAM GUA-CDs can load siRNA through the multiple hydrogen bonds between their guanidinium groups and phosphate groups in siRNA. Meanwhile, the amino acid groups at the edges of LAAM GUA-CDs endow them the capacity to target tumors. After loading siBcl-2 as a therapeutic agent, LAAM GUA-CDs/siBcl-2 has a high tumor inhibition rate of up to 68%, which is twice more than that of commercial Lipofectamine 2000. Furthermore, LAAM GUA-CDs do not cause side effect during antitumor treatment owing to their high tumor-targeting ability, thus providing a versatile strategy for tumor-targeted siRNA delivery and cancer therapy.
研究领域:
生物医学工程
·
分子生物学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 45
·期 42
·19812-19817
·
IF 3.591
Zhaomin Wang,Yong Liu,Weishan Wang,Chang Zhao,Weiying Lin
Fluorescent probes are a powerful tool in biological and biochemical fields. Herein, we prepared a new small molecule fluorescent probe PYQU as a robust tool that can explore the interaction between RNA and SO2 in biological environments. The probe PYQU could detect SO2 and RNA by a change in green and red fluorescence, respectively. Besides, the probe PYQU has excellent properties, such as low biological toxicity, good membrane permeability, and high selectivity. PYQU was used to detect SO2 in living cells and zebrafish in the green channel and visualize endogenous RNA of cells with a deep red fluorescence signal. Therefore, we believe that the probe PYQU is a valuable, robust, and reliable tool for studies of RNA and SO2.
研究领域:
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）