Journal of Materials Chemistry B
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2024
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IF 6.1
Yan Zhang,Qin LiMiao,Feng MengFan,Xianghui Yu,Yuqing Wu
Small interfering RNA (siRNA), comprising 21-23 nucleotides, functions by complementary binding to specific mRNA sequences, thereby suppressing target protein expression. Despite their vast potential in disease therapy, siRNAs face challenges due to their susceptibility to degradation and high electronegativity, rendering them unstable in the bloodstream and impeding their passage across endothelial barriers. Moreover, successful intracellular delivery necessitates overcoming endosomal entrapment, posing a significant hurdle for carrier material development. In this study, leveraging the strong affinity of histidine oligomers (His6) for metal ions, we engineered nanoparticles (HmA) by gentle assembly with divalent zinc ions under pH=8 conditions. We designed the RNA-binding functional peptide L2-NTD to enhance siRNA stability and delivery efficiency when complexed with HmA. The resulting siRNA+L2-NTD@HmA nanoparticles were formed via in situ encapsulation, ensuring efficient siRNA delivery into cells with minimal cytotoxicity and degradation. This approach presents a novel strategy for the design and artificial fabrication of carriers for effective RNA delivery.
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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.
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Science Advances
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2025
·Vol. 11
·期 34
·
IF 12.5
Zhiyi Wang,Jingyi Zhang,Jilei Huang,Gan Sha,Xinyue Song,Xue Cao,Zhenchen Yan,Chuanhe Liu,Siping Chen,Ziying Li,Xiuqin Huang,Qingjun Xie,Xin Yang,Guohui Zhou,Tong Zhang
RNA viruses often remodel host intracellular membranes to establish specialized replication compartments through viral protein–induced phase separation. However, the mechanisms underlying membrane remodeling and the characteristics that render these sites conducive to replication remain poorly understood, particularly in plant negative-strand RNA viruses. Here, we demonstrate that the phosphoprotein (P) of rice stripe mosaic virus (RSMV) forms biomolecular condensates via liquid-liquid phase separation (LLPS) to recruit essential components for viral replication factories (VFs). We identify a direct interaction between RSMV P and adenosine diphosphate (ADP) ribosylation factor 1 (OsARF1C), a crucial regulator of the coatomer protein I (COP I) vesicle transport pathway that is vital for viral replication. This interaction indirectly recruits OsARF1C’s partner, phosphatidylinositol 4-kinase beta (OsPI4KB), which drives localized phosphatidylinositol-4 phosphate (PI4P) synthesis. Concurrently, the P protein modulates its aggregates and LLPS droplets through PI4P, thereby expanding the replication site and enhancing viral replication.
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Data
·
2025
·Vol. 11
·期 1
·4
·
IF 2
Nataliya G. Luzgina,Svetlana N. Tarbeeva,Daniil D. Romashin,Konstantin G. Ptitsyn,Svetlana A. Khmeleva,Leonid K. Kurbatov,Sergey P. Radko,Anna S. Kozlova,Polina A. Veselova,Ekaterina V. Ilgisonis,Alexander L. Rusanov
The aryl hydrocarbon receptor (AhR) plays a crucial role in mediating xenobiotic responses, as well as regulating broader metabolic, differentiation, and stress response programs. In this study, we present a comprehensive long-read RNA sequencing dataset that examines transcriptional changes in the HepaRG human cell line during differentiation induced by dimethyl sulfoxide (DMSO) and acute activation of the AhR with 3-methylcholanthrene (3-MC). We identified 946 genes that were differentially expressed between the NonDiff and Diff conditions (303 genes upregulated and 643 genes downregulated), and 1786 genes that showed differential expression between Diff and Ind conditions (961 genes upregulated and 825 genes downregulated). The acute induction of 3-MC produced a robust AhR signature, characterized by the robust induction ofCYP1A1andCYP1B1, along with a coordinated downregulation of several constitutive hepatic genes involved in drug metabolism (e.g.,CYP3A4andCYP2C8). To facilitate further analysis and reuse of our data, we have provided processed gene-level count matrices, transcript per million (TPM) tables, and detailed differential expression results, as well as analysis scripts. This resource supports research into AhR biology, pharmacogene regulation, and the development of methods for long-read transcriptomics in liver models.Dataset:https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1366635Dataset License:CC-BY 4.0
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MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2022
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IF 4.369
Yuanfei Ren,Maowei Yang,Xindong Wang,Buxuan Xu,Zerong Xu,Bo Su
Diabetic osteoporosis (DOP) is a complication of diabetes mellitus (DM) and occurs due to alterations in bone metabolism under hyperglycemic condition. ELAV-like RNA binding protein 1 (ELAVL1) is abnormally up-regulated in diabetes-related diseases. Bioinformatics prediction indicates that divalent metal transporter 1 (DMT1) is a potential target of ELAVL1 . To explore the role of ELAVL1 and the involvement of ELAVL1/DMT1 axis in DOP, we established a mouse model of DM by administration of high-fat diet and intraperitoneal injection with streptozotocin (STZ). The expression of ELAVL1 and DMT1 was increased in the bone tissues of DM mice. Knockdown of ELAVL1 reduced iron level and oxidative stress , promoted osteogensis, and prevented bone mass loss, thus mitigating DOP in DM mice. In vitro , mouse pre-osteoblast MC3T3-E1 cells were treated with high glucose (25 mM) and ferric ammonium citrate (FAC, 200 μM). The inhibitory effects of ELAVL1 knockdown on iron accumulation and oxidative stress were evidenced in MC3T3-E1 cells. Knockdown of ELAVL1 enhanced osteoblast viability, differentiation and mineralization . Notably, the expression of DMT1 was positively correlated with that of ELAVL1 in vivo and in vitro . Overexpression of DMT1 abolished the effect of ELAVL1 knockdown on the behaviors of MC3T3-E1 cells, suggesting that ELAVL1 might function through regulating DMT1. In conclusion, knockdown of ELAVL1 likely alleviated DOP by inhibiting iron overload and oxidative stress and promoting osteogenesis, and DMT1 might be involved in this process. These findings provide insights into the pathogenesis of DOP and suggest a potential therapeutic target for DOP treatment.
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Journal of Cancer
·
2019
·
IF 3.182
Huaizeng Chen,Jia Liu,Hanzhi Wang,Qi Cheng,Caiyun Zhou,Xiaojing Chen,Feng Ye
Background and Aims: Ovarian carcinoma (OC) is one of the most lethal malignant tumors with a high reoccurrence and chemoresistance. The key mechanism relationship with chemoresistance in ovarian carcinoma is still unclear. The existence of cancer stem cells involves in chemoresistance and reoccurrence in OC. The objective of this study was to investigate the expression, suppression of malignant properties and reversal of paclitaxel resistance inhibiting RNA-binding protein Musashi-1 with siRNA in ovarian cancer cells. Methods: The expression of MSI-1 was analyzed in 39 normal ovarian epithelia tissues, 92 serous cystadenomas, 68 borderline serous cystadenomas, and 97 serous cystadenocarcinomas by immunohistochemistry. pLKO.1-MSI-1-siRNA expression vector was transfected into ovarian carcinoma cell line A2780 and its paclitaxel-resistant cell subline A2780/Taxol. The roles of MSI-1 in proliferation, apoptosis, migration and invasion were explored by cell proliferation analysis, Caspase 3 activity assay, wound healing assay, migration and matrigel invasion assay, respectively. Western Blotting and Real-time quantitative PCR were conducted to detect the expression of MSI-1 and the ERK signaling pathway. Reversal of paclitaxel resistance assay was used to evaluate the role of MSI-1 in paclitaxel resistance of OC cells. Finally, therapeutic effects of MSI-1 inhibition were investigated the xenogratfs of SCID mice in vivo of the paclitacel-resistant. Results: MSI-1 is overexpressed and associated with an unfavorable prognosis in OC patients. Knockdown of MSI-1 by small interfering RNA (siRNA) inhibits proliferation, promotes apoptosis, and reduces migration and invasion of cancer cells. Moreover, MSI-1 expression inhibition reverses paclitaxel-resistance in OC cells. We further display that MSI-1 effectively protects OC cells from paclitaxel-induced apoptosis by increasing the expression of p-Bcl-2 through ERK signaling pathway activation. In vivo , MSI-1 siRNA clearly showed a strong effect on tumor growth inhibition and paclitaxel-resistance reversal. Conclusions: These findings suggest that MSI-1 overexpression is associated with the prognosis of OC patients, and knockdown of MSI-1 can suppress malignant properties and reverse paclitaxel-resistance in OC cells. MSI-1 maybe act as a potential prognostic indicator and a therapeutic target in OC.
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Autophagy
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2018
·
IF 11.1
Li Yang,Bing Han,Yuan Zhang,Ying Bai,Jie Chao,Gang Hu,Honghong Yao
Endothelial-mesenchymal transition (EndoMT) is associated with damage to blood-brain barrier (BBB) integrity. Circular RNAs (circRNAs) are highly expressed in the brain and are involved in brain diseases; however, whether circRNAs regulate the EndoMT in the brain remains unknown. Our study demonstrated that circHECW2 regulated the EndoMT by directly binding to MIR30D, a significantly downregulated miRNA from miRNA profiling, which subsequently caused an increased expression of ATG5. These findings shed new light on the understanding of the noncanonical role of ATG5 in the EndoMT induced by methamphetamine (Meth) or lipopolysaccharide (LPS). The in vivo relevance was confirmed as microinjection of circHecw2 siRNA lentivirus into the mouse hippocampus suppressed the EndoMT induced by LPS. These findings provide novel insights regarding the contribution of circHECW2 to the nonautophagic role of ATG5 in the EndoMT process in the context of drug abuse and the broad range of neuroinflammatory disorders.
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ACS Synthetic Biology
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2025
·
IF 3.9
Jing Wu,Ziqian Xiao,Yuhui Du,Minglan Luo,Jiacheng Zhang,Pei Guo,Zhipeng Chen,Binyuan Yang,Tingjian Chen
Aptamer-based sensors (aptasensors) have been extensively employed in biosensing and diagnostics. However, the broader application of aptasensors fabricated with DNA and RNA aptamers has been limited due to the intolerance of DNA and RNA to nucleases in biological fluids. A majority of sugar-modified nucleic acids, in particular 2’-F and 2’-OMe-modified nucleic acids, demonstrate a remarkable resistance to nuclease degradation and thus hold great potential in the development of more stable aptamers and aptasensors. In this work, employing enzymes including a laboratory-evolved polymerase for 2’-modified nucleic acids, we carried out systematic evolution of ligands by exponential enrichment (SELEX) experiments to obtain 2’-F/OMe-RNA aptamers for Bacillus cereus 5/B/6 metallo-β-lactamase (B. cereus 5/B/6 MBL), a crucial marker of many penicillin-resistant strains. Three aptamers composed of 2’-OMe-A, 2’-F-U, 2’-F-C, and 2’-OMe-G nucleotides (Apt-FUC1, Apt-FUC2, and Apt-FUC3) have been obtained and systematically characterized. All of them exhibited excellent target binding affinities, with equilibrium dissociation constant (Kd ) values of 95.9, 70.0, and 81.3 nM, and outstanding biological stability. Combining FAM-labeled Apt-FUC1, Apt-FUC2, and Apt-FUC3 with graphene oxide (GO), which could quench the fluorescence of FAM, we successfully constructed three sensitive and biologically stable 2’-F/OMe-RNA aptasensors for B. cereus 5/B/6 MBL, with the limit of detection (LOD) values of 0.38, 0.27, and 0.29 nM. Moreover, these three aptasensors all demonstrated good specificity for target detection in biological samples. This work has established a streamlined strategy for generating stable 2’-F/OMe-RNA aptamers and aptasensors, which should broaden the application of sugar-modified nucleic acids in biosensing and diagnostics.
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Food Bioscience
·
2025
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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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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.
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ANALYTICAL CHEMISTRY
·
2018
·
IF 6.042
Yunying Cheng,Chunmei Li,Ruizhu Mu,Yuanfang Li,Tiantian Xing,Binbin Chen,Chengzhi Huang
Cellular RNA dynamics are closely associated with a vast range of physiological processes that are mostly long-lasting. To uncover the association between RNA dynamics and these processes, fluorescent RNA probes with high specificity, photostability, and biocompatibility are compulsory. Herein, a series of fluorescent carbon dots (CDs) have been prepared by one-pot hydrothermal treatment of o-, m-, or p-phenylenediamines with triethylenetetramine. Only CDs derived from the meta precursor (m-CDs) with excellent photostability and biocompatibility can specifically bind to cellular RNA, allowing successfully long-term (up to 3 days) monitoring of RNA dynamics during cell apoptosis, mitosis, and proliferation. This RNA affinity can be attributed to the isoquinoline moieties and amines on the surface of m-CDs, which can bind to RNA through π–π stacking and electrostatic bonding, respectively. The cellular internalization of m-CDs is time-, temperature-, ATP-, caveolar, and microtubule-dependent. Additionally, investigations on the in vivo behavior of m-CD suggest that they can be efficiently and rapidly excreted from the zebrafish larvae body after 48 h. Our results provide a powerful tool for clarifying complex relationships between RNA dynamics and basic biological processes, disease development, or drug interactions.
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BIOSENSORS & BIOELECTRONICS
·
2021
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IF 10.618
Yuqian Liu,Ruyi Li,Fangyuan Liang,Chao Deng,Farzad Seidi,Huining Xiao
Demand on the quick screening of gastric cancer (GC) has significantly stimulated the development of biomarker sensing techniques. Herein, we report the novel fluorescent paper-based analytical devices (PADs) for detections of GC-related microRNA-21 (miRNA-21) and circular RNA from Hippocampus Abundant Transcript 1 gene (circRNA-HIAT1) with prominent reliability and sensitivity. The PADs, constructed by in-situ synthesis of blue-emissive carbon dots (CDs) and conjugations of probe DNAs , exhibit the superior uniformity and stability. In the presence of targets, rolling circle amplifications (RCA) are triggered to generate long DNA strands for the assemblies of green-/red-emissive labels. Consequently, remarkable blue-to-green and blue-to-red emission color transitions of the PADs are achieved, implementing the color-analysis of miRNA-21 and circRNA-HIAT1, respectively. Benefited from the efficient RCA, coupled with the drastic ratiometric fluorescent changes, the limit of detections (LODs) of PADs are found to be several fM with the upper limit of the linear detection range at 1 nM. More importantly, the fluorescent PADs possess excellent specificity, as well as anti-interference capability in biological settings, enabling their applications in accurate GC screening with plasma samples. Overall, the proposed fluorescent PADs are featured with robust sensing platform, facile signal readout, and exceptional dual-type RNA sensing performance, holding high potential in point-of-care testing (POCT).
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