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  1. Article ; Online: Targeting m6A modification inhibits herpes virus 1 infection

    Zhuoying Feng / Fanghang Zhou / Miaomiao Tan / Tingting Wang / Ying Chen / Wenwen Xu / Bin Li / Xin Wang / Xin Deng / Ming-Liang He

    Genes and Diseases, Vol 9, Iss 4, Pp 1114-

    2022  Volume 1128

    Abstract: The latent infection by herpes virus type 1 (HSV-1) may be lifelong in trigeminal ganglia and a suspected cause of Alzheimer's Disease (AD) and Amyotrophic lateral sclerosis (ALS). Whether and how N6-methyladenosine (m6A) modification of viral RNAs ... ...

    Abstract The latent infection by herpes virus type 1 (HSV-1) may be lifelong in trigeminal ganglia and a suspected cause of Alzheimer's Disease (AD) and Amyotrophic lateral sclerosis (ALS). Whether and how N6-methyladenosine (m6A) modification of viral RNAs affects virus infection are poorly understood. Here, we report that HSV-1 infection enhanced the expression of m6A writers (METTL3, METTL14) and readers (YTHDF1/2/3) at the early infection stage and decreased their expression later on, while suppressed the erasers' (FTO, ALBKH5) expression immediately upon infection to facilitate viral replication. Inhibiting m6A modification by 3-deazaadenosine (DAA) significantly decreased viral replication and reduced viral reproduction over 1000 folds. More interestingly, depleting the writers and readers by siRNAs inhibited virus replication and reproduction; whereas depleting the erasers promoted viral replication and reproduction. Silencing YTHDF3 strikingly decreased viral replication by up to 90%, leading to reduction of up to 10-fold viral replication and over 100-fold virus reproduction, respectively. Depletion of m6A initiator METTL3 (by 60%–70%) by siRNA correlatedly decreased viral replication 60%–70%, and reduced virus yield over 30-fold. Consistently, ectopic expression of METTL3 largely increased virus yield. METTL3 knockdown suppressed the HSV-1 intermediate early and early genes (ICP0, ICP8 and UL23) and late genes (VP16, UL44, UL49 and ICP47); while ectopic expression of METTL3 upregulated these gene expression. Results from our study shed the lights on the importance for m6A modification to initiate HSV-1 early replication. The components of m6A modification machinery, particularly m6A initiator METTL3 and reader YTHDF3, would be potential important targets for combating HSV-1 infections.
    Keywords Gene silencing ; HSV-1 infection ; m6A modification ; Virus replication ; Virus reproduction ; Medicine (General) ; R5-920 ; Genetics ; QH426-470
    Subject code 570
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Integrated regulatory network in Pseudomonas syringae reveals dynamics of virulence

    Xiaolong Shao / Miaomiao Tan / Yingpeng Xie / Chunyan Yao / Tingting Wang / Hao Huang / Yingchao Zhang / Yiqing Ding / Jingui Liu / Liangliang Han / Canfeng Hua / Xin Wang / Xin Deng

    Cell Reports, Vol 34, Iss 13, Pp 108920- (2021)

    2021  

    Abstract: Summary: Pseudomonas syringae, a Gram-negative plant pathogen, expresses multitudinous transcriptional regulators to control the type III secretion system (T3SS) and response to diverse environmental challenges. Although the mechanisms of virulence- ... ...

    Abstract Summary: Pseudomonas syringae, a Gram-negative plant pathogen, expresses multitudinous transcriptional regulators to control the type III secretion system (T3SS) and response to diverse environmental challenges. Although the mechanisms of virulence-associated regulators of P. syringae have been studied for decades, the overall crosstalk underlying these regulators is still elusive. Here, we identify five T3SS regulators (EnvZ-OmpR, CbrAB2, PhoPQ, PilRS, and MgrA), and find that the two-component systems EnvZ-OmpR and CbrAB2 negatively regulate the T3SS. To elucidate crosstalk between 16 virulence-associated regulators in P. syringae, we map an online intricate network called “PSRnet” (Pseudomonas syringae regulatory network) by combining the differentially expressed genes (DEGs) of these 16 regulators by RNA sequencing (RNA-seq) and their binding loci by chromatin immunoprecipitation sequencing (ChIP-seq). Consequently, we identify 238 and 153 functional genes involved in the T3SS and other virulence-related pathways in KB and MM media, respectively. Our results provide insights into the mechanism of plant infections caused by P. syringae.
    Keywords Pseudomonas syringae ; transcriptional regulator ; type III secretion system ; crosstalk ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Expression of Cry1Ab and Cry2Ab by a polycistronic transgene with a self-cleavage peptide in rice.

    Qichao Zhao / Minghong Liu / Miaomiao Tan / Jianhua Gao / Zhicheng Shen

    PLoS ONE, Vol 9, Iss 10, p e

    2014  Volume 110006

    Abstract: Insect resistance to Bacillus thuringiensis (Bt) crystal protein is a major threat to the long-term use of transgenic Bt crops. Gene stacking is a readily deployable strategy to delay the development of insect resistance while it may also broaden ... ...

    Abstract Insect resistance to Bacillus thuringiensis (Bt) crystal protein is a major threat to the long-term use of transgenic Bt crops. Gene stacking is a readily deployable strategy to delay the development of insect resistance while it may also broaden insecticidal spectrum. Here, we report the creation of transgenic rice expressing discrete Cry1Ab and Cry2Ab simultaneously from a single expression cassette using 2A self-cleaving peptides, which are autonomous elements from virus guiding the polycistronic viral gene expression in eukaryotes. The synthetic coding sequences of Cry1Ab and Cry2Ab, linked by the coding sequence of a 2A peptide from either foot and mouth disease virus or porcine teschovirus-1, regardless of order, were all expressed as discrete Cry1Ab and Cry2Ab at high levels in the transgenic rice. Insect bioassays demonstrated that the transgenic plants were highly resistant to lepidopteran pests. This study suggested that 2A peptide can be utilized to express multiple Bt genes at high levels in transgenic crops.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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