MOLECULAR PLANT PATHOLOGY
·
2024
·Vol. 25
·期 1
·e13416
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IF 4.8
Wanyue Li,Zeming Liu,Yuli Huang,Jie Zheng,Yang Yang,Yimeng Cao,Liwen Ding,Yuling Meng,Weixing Shan
Phytophthora infestans is a destructive oomycete that causes the late blight of potato and tomato worldwide. It secretes numerous small proteins called effectors in order to manipulate host cell components and suppress plant immunity. Identifying the targets of these effectors is crucial for understanding P. infestans pathogenesis and host plant immunity. In this study, we show that the virulence RXLR effector Pi23014 of P. infestans targets the host nucleus and chloroplasts. By using a liquid chromatogrpahy-tandem mass spectrometry assay and co-immunoprecipitation assasys, we show that it interacts with NbRBP3a, a putative glycine-rich RNA-binding protein. We confirmed the co-localization of Pi23014 and NbRBP3a within the nucleus, by using bimolecular fluorescence complementation. Reverse transcription-quantitative PCR assays showed that the expression of NbRBP3a was induced in Nicotiana benthamiana during P. infestans infection and the expression of marker genes for multiple defence pathways were significantly down-regulated in NbRBP3 -silenced plants compared with GFP -silenced plants. Agrobacterium tumefaciens -mediated transient overexpression of NbRBP3a significantly enhanced plant resistance to P. infestans . Mutations in the N-terminus RNA recognition motif (RRM) of NbRBP3a abolished its interaction with Pi23014 and eliminated its capability to enhance plant resistance to leaf colonization by P. infestans . We further showed that silencing NbRBP3 reduced photosystem II activity, reduced host photosynthetic efficiency, attenuated Pi23014-mediated suppression of cell death triggered by P. infestans pathogen-associated molecular pattern elicitor INF1 , and suppressed plant immunity.
研究领域:
植物病理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Shuangping Ma,Xianting Liu,Yiran Qin,Yilong Wang,Yu Feng,Binfeng Cheng,Lei Wang
Sickle cell disease (SCD) and β-thalassemia are autosomal recessive genetic disorders caused by abnormal synthesis of β-globin chains. Reversing the transition of fetal-to-adult hemoglobin after birth shows great potential in the treatment of these disorders. Here, we identified an RNA-binding protein, RBM3, as a novel HbF (HbF, α 2 γ 2 ) suppressor. Specifically, downregulation of RBM3 in the erythroid progenitor cell line HUDEP-2 robustly induced γ-globin expression at both the mRNA and protein levels, with a slight impact on β-globin levels. Conversely, overexpression of RBM3 in HUDEP-2 cells led to a marked reduction in γ-globin expression. According to the previous study, we introduced specific inhibitors targeting FAK and Src to block RBM3 protein synthesis. Surprisingly, treatment with the FAK inhibitor resulted in a significant increase in γ-globin expression, whereas the Src inhibitor had little effect. Mechanistically, RBM3 depletion accelerated the degradation of BCL11A protein at the post-transcriptional level, without affecting its mRNA stability. Moreover, RBM3 silencing restricted the overall translation efficiency while selectively lifting the ratio of γ-globin mRNA in polysomes. Importantly, downregulation of RBM3 did not impair erythropoiesis progression, suggesting a safe and effective therapeutic strategy for SCD and β-thalassemia. Our findings identify RBM3 as a negative regulator of HbF expression and reveal it as a novel molecular target for modulating the fetal-to-adult hemoglobin switch, holding great promise for the treatment of SCD and β-thalassemia.
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产品关联
DOI
PubMed
高影响因子
Biochemistry and Cell Biology
·
2023
·Vol. 102
·期 1
·
IF 2.9
Bin Zhang,Ruowen Sun,Min Gu,Zehui Jiang,Ye Wang,Linlin Zhang,Xiaoyang Liu,Zuofei Chi
Acute T-lymphocyte leukemia (T-ALL) is a malignant tumor disease. RNA-binding protein neotumor ventral antigen-1 (NOVA1) is highly expressed in bone marrow mononuclear cells of T-ALL patients, while the role of NOVA1 in T-ALL progression remains unknown. The gain- and loss-of-function studies for NOVA1 were performed in Jurkat and CCRF-CEM cells. NOVA1 overexpression promoted cell proliferation and cell cycle progression. NOVA1 knockdown increased the apoptosis rate of T-ALL cells. Ubiquitin-specific protease 44 (USP44), a nuclear protein with deubiquitinase catalytic activity, has been reported to play an oncogene role in human T-cell leukemia. USP44 expression was positively associated with NOVA1, and RNA immunoprecipitation assay verified the binding of NOVA1 to the mRNA of USP44. USP44 knockdown partially abolished NOVA1-induced cell proliferation and inhibition of apoptosis. The in vivo xenograft experiment was performed by injection of T-ALL tumor cells into the tail vein of NOD/SCID mice. The knockdown of NOVA1 had lower tumorigenicity. NOVA1 knockdown alleviated pathological changes in lung and spleen tissues, and increased the overall survival period and the weight of T-ALL mice. Thus, NOVA1 acts as an accelerator in T-ALL, and its function might be achieved by binding to and stabilizing USP44 mRNA.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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DOI
PubMed
高影响因子
CANCER RESEARCH
·
2024
·
IF 12.5
Fang Liang,Zhang Li,Wang Mengran,He Yuhao,Yang Jiao,Huang Zengjin,Tan Ying,Fang Ke,Li Jun,Sun Zhiyuan,Li Yanping,Tang Yisen,Liang Weizheng,Cui Huanhuan,Zhu Qionghua,Wu Zhe,Li Yiming,Hu Yuhui,Chen Wei
Epithelial-mesenchymal transition (EMT) is a fundamental cellular process frequently hijacked by cancer cells to promote tumor progression, especially metastasis. EMT is orchestrated by a complex molecular network acting at different layers of gene regulation. In addition to transcriptional regulation, post-transcriptional mechanisms may also play a role in EMT. Here, we performed a pooled CRISPR screen analyzing the influence of 1547 RNA binding proteins (RBPs) on cell motility in colon cancer cells and identified multiple core components of P-bodies (PBs) as negative modulators of cancer cell migration. Further experiments demonstrated that PB depletion by silencing DDX6 or EDC4 could activate hallmarks of EMT thereby enhancing cell migration in vitro as well as metastasis formation in vivo. Integrative multi-omics analysis revealed that PBs could repress the translation of the EMT-driver gene HMGA2, which contributed to PB-meditated regulation of EMT. This mechanism is conserved in other cancer types. Furthermore, endoplasmic reticulum (ER) stress was an intrinsic signal that induced PB disassembly and translational derepression of HMGA2. Taken together, this study has identified a function of PBs in regulation of EMT in cancer.
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
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遗传学
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DOI
PubMed
高影响因子
ACS Sensors
·
2025
·
IF 9.1
Qiuhao Xu,Yanxin Wang,Yingyu Zhu,Tan Wang,Yuan Rao,Xiaoping Gan,Yingcui Bu
Real-time monitoring of the dynamics and heterogeneity of mitochondria and nucleoli is essential for a comprehensive understanding of cellular homeostasis and pathological mechanisms. However, current approaches mainly suffer from two major limitations: (1) Limited permeability through nuclear pore complexes (NPCs) in live cells and (2) vulnerability of intensity-based detection methods to interference from the cellular microenvironment. To overcome these challenges, a red-emissive fluorescent probe (DSM) with high photostability was developed by strategically tuning the π-conjugation between electron-donating and accepting moieties. Gratifyingly, DSM can selectively accumulate in both mitochondria and nucleoli with a distinguishable average fluorescence lifetime after binding with RNA and protein, which enables their dynamic visualization of morphological changes and interplay during oxidative stress by fluorescence lifetime imaging microscopy (FLIM). This research not only paves a new pathway for real-time imaging the physiology of mitochondria and nucleoli but also inspires to guide the pathological study of related diseases.
研究领域:
细胞生物学
·
生物成像
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荧光显微镜
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分子生物学
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生物物理学
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产品关联
DOI
PubMed
高影响因子
iScience
·
2022
·
IF 6.107
Fanyang Lv,Yuhua Zhan,Wei Lu,Xiubin Ke,Yahui Shao,Yiyuan Ma,Juan Zheng,Zhimin Yang,Shanshan Jiang,Liguo Shang,Yao Ma,Lei Cheng,Claudine Elmerich,Yongliang Yan,Min Lin
Summary Bacteria of the genus Pseudomonas consume preferred carbon substrates in nearly reverse order to that of enterobacteria, and this process is controlled by RNA-binding translational repressors and regulatory ncRNA antagonists. However, their roles in microbe-plant interactions and the underlying mechanisms remain uncertain. Here we show that root-associated diazotrophic Pseudomonas stutzeri A1501 preferentially catabolizes succinate, followed by the less favorable substrate citrate, and ultimately glucose. Furthermore, the Hfq/Crc/CrcZY regulatory system orchestrates this preference and contributes to optimal nitrogenase activity and efficient root colonization. Hfq has a central role in this regulatory network through different mechanisms of action, including repressing the translation of substrate-specific catabolic genes, activating the nitrogenase gene nifH posttranscriptionally, and exerting a positive effect on the transcription of an exopolysaccharide gene cluster. Our results illustrate an Hfq-mediated mechanism linking carbon metabolism to nitrogen fixation and root colonization, which may confer rhizobacteria competitive advantages in rhizosphere environments.
研究领域:
微生物学
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植物科学
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分子生物学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Yi He,Lejia Zhang,Siyuan Huang,Yuquan Tang,Yiming Li,Hongyu Li,Guanhui Chen,Xun Chen,Xiliu Zhang,Wei Zhao,Feilong Deng,Dongsheng Yu
Background The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism.Methods The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites.Results We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites.Conclusion We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects.
研究领域:
生物材料
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组织工程
·
骨再生
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分子生物学
·
纳米技术
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DOI
PubMed
高影响因子
MOLECULAR CARCINOGENESIS
·
2024
·
IF 3
Beibei Wang,Xin Fan,Lingang Wang,Xiaosong Wei
Sorbin and SH3 domain-containing 2 (SORBS2) is an RNA-binding protein and has been implicated in the development of some cancers. However, its role in bladder cancer (BC) is yet to be established. The expression of SORBS2 in BC tissues was determined from the Gene Expression Omnibus and Gene Expression Profiling Interactive Analysis databases and collected paired tumor/normal samples. The effects of SORBS2 on BC cells were detected by CCK-8, colony formation, Transwell, dual-luciferase, RNA immunoprecipitation, chromatin immunoprecipitation, and DNA pull-down assays. In vivo, BC cell growth and metastasis were studied by a xenograft subcutaneous model and a tail-vein metastasis model. The results showed that SORBS2 expression was significantly decreased in BC tissues and cells. SORBS2 overexpression inhibited cell proliferation, migration, invasion, and epithelial–mesenchymal transition in vitro and tumor growth and metastasis in vivo, while silencing SORBS2 produced the opposite effect. Mechanistically, we found that SORBS2 enhanced the stability of tissue factor pathway inhibitor (TFPI) mRNA via direct binding to its 3′ UTR. Restoration of TFPI expression reversed SORBS2 knockdown-induced malignant phenotypes of BC cells. In addition, SORBS2 expression was negatively regulated by the transcription factor specificity protein 1 (SP1). Conversely, SORBS2 can be transcriptionally regulated by SP1 and inhibit BC cell growth and metastasis via stabilization of TFPI mRNA, indicating SORBS2 may be a promising therapeutic target for BC.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
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