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AtVQ25 promotes salicylic acid-related leaf senescence by fine-tuning the self-repression of AtWRKY53

Journal of Integrative Plant biology 2024年第6期66卷 1126-1147页

作者： Qi Tan Mingming Zhao Jingwei Gao Ke Li Mengwei Zhang Yunjia Li Zeting Liu Yujia Song Xiaoyue Lu Zhengge Zhu Rongcheng Lin Pengcheng Yin Chunjiang Zhou Geng Wang Ministry of Education Key Laboratory of molecular and cellular biology Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell Signaling and Environmental Adaptation Hebei Key Laboratory of Molecular and Cellular Biology College of Life Sciences Hebei Normal University College of Chemical Engineering Shijiazhuang University institute of Botany Chinese Academy of Sciences

Most mechanistic details of chronologically ordered regulation of leaf senescence are unknown.Regulatory networks centered on AtWRKY53 are crucial for orchestrating and integrating various senescence-related signals. Notably, AtWRKY53binds to its own promoter and represses transcription of AtWRKY53, but the biological significance and mechanism underlying this selfrepression remain unclear. In this study, we identified the VQ motif-containing protein AtVQ25as a cooperator of AtWRKY53. The expression level of AtVQ25 peaked at mature stage and was specifically repressed after the onset of leaf senescence. AtVQ25-overexpressing plants and atvq25 mutants displayed precocious and delayed leaf senescence, respectively. Importantly, we identified AtWRKY53 as an interacting partner of AtVQ25. We determined that interaction between AtVQ25 and AtWRKY53 prevented AtWRKY53from binding to W-box elements on the AtWRKY53promoter and thus counteracted the selfrepression of AtWRKY53. In addition, our RNA-sequencing data revealed that the AtVQ25-AtWRKY53 module is related to the salicylic acid(SA) pathway. Precocious leaf senescence and SA-induced leaf senescence in AtVQ25-overexpressing lines were inhibited by an SA pathway mutant, atsid2, and Nah G transgenic plants; AtVQ25-overexpressing/atwrky53 plants were also insensitive to SA-induced leaf senescence. Collectively, we demonstrated that AtVQ25 directly attenuates the self-repression of AtWRKY53 during the onset of leaf senescence,which is substantially helpful for understanding the timing of leaf senescence onset modulated by AtWRKY53.

关键词： AtWRKY53 leaf senescence salicylic acid transcriptional regulation VQ motif-containing proteins

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Exploring noncoding variants in genetic diseases:from detection to functional insights

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Journal of Genetics and Genomics 2024年第2期51卷 111-132页

作者： Ke Wu Fengxiao Bu Yang Wu Gen Zhang Xin Wang Shunmin He Mo-Fang Liu Runsheng Chen Huijun Yuan institute of Rare Diseases West China Hospital of Sichuan UniversityChengduSichuan 610041China Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang 310024China Key Laboratory of RNA biology Center for Big Data Research in HealthInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of molecular biology State Key Laboratory of Cell BiologyShanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China

Previous studies on genetic diseases predominantly focused on protein-coding variations, overlooking the vast noncoding regions in the human genome. The development of high-throughput sequencing technologies and functional genomics tools has enabled the systematic identification of functional noncoding variants. These variants can impact gene expression, regulation, and chromatin conformation, thereby contributing to disease pathogenesis. Understanding the mechanisms that underlie the impact of noncoding variants on genetic diseases is indispensable for the development of precisely targeted therapies and the implementation of personalized medicine strategies. The intricacies of noncoding regions introduce a multitude of challenges and research opportunities. In this review, we introduce a spectrum of noncoding variants involved in genetic diseases, along with research strategies and advanced technologies for their precise identification and in-depth understanding of the complexity of the noncoding genome. We will delve into the research challenges and propose potential solutions for unraveling the genetic basis of rare and complex diseases.

关键词： Noncoding variation Genetic disease Research approach Challenge

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Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis

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Asian Journal of Andrology 2024年第2期26卷 212-219页

作者： Gao-Qing Qian Xiao-Chen Wang Xi Zhang Bin Shen Qiang Liu State Key Laboratory of Reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjing 211166China Shanghai Key Laboratory of Reproductive Medicine Department of HistoembryologyGenetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China State Key Laboratory of molecular biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Male germ cells employ specific metabolic pathways throughout their developmental stages.In a previous study,we discovered heightened expression of pyruvate kinase M(PKM),a pivotal glycolytic enzyme,in spermatogonia and spermatids.To gain deeper insights into PKM's roles in spermatogenesis,sperm function,and male fertility,we engineered a conditional-knockout mouse model(Pkm-vkO mice)to selectively disrupt the Pkm gene within germ cells.Despite maintaining regular testicular histology and sperm morphology,the male Pkm-vko mice were infertility,characterized by significant impairments in sperm motility and adenosine triphosphate(ATP)generation.In addition,Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation,as well as compromised performance in in vitro fertilization experiments.To conclude,PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells;however,it emerges as a critical factor influencing sperm motility and overall male fertility.

关键词： glycolysis male fertility pyruvate kinase M sperm motility spermatogenesis

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Host cyclophilin A facilitates SARS-CoV-2 infection by binding and stabilizing spike on virions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 36-39页

作者： Xiangpeng Sheng Fang Zhu Hong Peng Fan Yang Yi Yang Cong Yang Zhen Wang Wei Chen Deyin Guo Ronggui Hu State Key Laboratory of molecular biology Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghaiChina MOE Key Laboratory of Tropical Disease Control Centre for Infection and Immunity StudySchool of MedicineSun Yat-sen UniversityShenzhenChina ICU Longhua Hospital Shanghai University of Traditional Chinese MedicineShanghaiChina

Dear Editor,The novel coronavirus SARS-CoV-2 rapidly evolutes to increase its infectivity and transmissibility,facilitates its immune escape,impairs vaccine efficacy,and currently causes repeated infections in human,which is mainly determined by the accumulated mutations in spike(S).1 Transmembrane S is a heavily glycosylated protein on the surface of the virion as homotrimer,responsible for binding to human angiotensin-converting enzyme 2(hACE2)receptor.2 While the architecture of S trimers has been well studied,how the stability of S is regulated by potential host factors remains unknown.

关键词： ACE2 vaccine infection

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Opto-fluidically multiplexed assembly and micro-robotics

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Light(Science & Applications) 2024年第3期13卷 544-554页

作者： Elena Erben Weida Liao Antonio Minopoli Nicola Maghelli Eric Lauga Moritz Kreysing Max Planck institute of molecular cell biology and Genetics Dresden 01307Germany Center for Systems biology Dresden 01307Germany institute of Biological and Chemical Systems–Biological Information Processing.Karlsruhe institute of Technology(KIT) Eggenstein-Leopoldshafen 76344Germany Department of Applied Mathematics and Theoretical Physics University of CambridgeCambridge CB30WAUK

Techniques for high-definition micromanipulations,such as optical tweezers,hold substantial interest across a wide range of disciplines.However,their applicability remains constrained by material properties and laser exposure.And while microfluidic manipulations have been suggested as an alternative,their inherent capabilities are limited and further hindered by practical challenges of implementation and control.Here we show that the iterative application of laser-induced,localized flow fields can be used for the relative positioning of multiple micro-particles,irrespectively of their material properties.Compared to the standing theoretical proposal,our method keeps particles mobile,and we show that their precision manipulation is non-linearly accelerated via the multiplexing of temperature stimuli below the heat diffusion limit.The resulting flow fields are topologically rich and mathematically predictable.They represent unprecedented microfluidic control capabilities that are illustrated by the actuation of humanoid micro-robots with up to 30 degrees of freedom,whose motions are sufficiently well-defined to reliably communicate personal characteristics such as gender,happiness and nervousness.Our results constitute high-definition micro-fluidic manipulations with transformative potential for assembly,micro-manufacturing,the life sciences,robotics and optohydraulically actuated micro-factories.

关键词： manipulation fluid assembly

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Defining two subpopulations of marginal zone B cells

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cellular & molecular Immunology 2024年第4期21卷 412-413页

作者： Xiaojing Liu Fei-Long Meng Key Laboratory of RNA Science and Engineering Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai200031China

Marginal zone(MZ)B cells,which are composed of heterogeneous subpopulations,are participate in the rapid response to antigens.Lee et al.showed that MZ B cells can be divided into two distinct subpopulations based on CD80 expression.These two subpopulations of MZ B cells exhibit differential autoreactivity,radiosensitivity,and functional capacities.

关键词： expression. subpopulations al.

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RACK1A promotes hypocotyl elongation by scaffolding light signaling components in Arabidopsis

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Journal of Integrative Plant biology 2024年第5期66卷 956-972页

作者： Yajuan Fu Wei Zhu Yeling Zhou Yujing Su Zhiyong Li Dayan Zhang Dong Zhang Jinyu Shen Jiansheng Liang Key Laboratory of molecular Design for Plant cell Factory of Guangdong Higher Education institutes Department of BiologySchool of Life SciencesInstitute of Plant and Food SciencesSouthern University of Science and TechnologyShenzhen 518055China

Plants deploy versatile scaffold proteins to intricately modulate complex cell signaling.Among these,RACK1A(Receptors for Activated C Kinase 1A)stands out as a multifaceted scaffold protein functioning as a central integrative hub for diverse signaling pathways.However,the precise mechanisms by which RACK1A orchestrates signal transduction to optimize seedling development remain largely unclear.Here,we demonstrate that RACK1A facilitates hypocotyl elongation by functioning as a flexible platform that connects multiple key components of light signaling pathways.RACK1A interacts with PHYTOCHROME INTERACTING FACTOR(PIF)3,enhances PIF3 binding to the promoter of BBX11 and down-regulates its transcription.Furthermore,RACK1A associates with ELONGATED HYPOCOTYL 5(HY5)to repress HY5 biochemical activity toward target genes,ultimately contributing to hypocotyl elongation.In darkness,RACK1A is targeted by CONSTITUTIVELY PHOTOMORPHOGENIC(COP)1 upon phosphorylation and subjected to COP1-mediated degradation via the 26 S proteasome system.Our findings provide new insights into how plants utilize scaffold proteins to regulate hypocotyl elongation,ensuring proper skoto-and photo-morphogenic development.

关键词： Arabidopsis hypocotyl development light signaling components RACK1 scaffoldprotein

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In-situ synthesis of quantum dots in the nucleus of live cells

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National Science Review 2024年第3期11卷 172-182页

作者： Yusi Hu Zhi-Gang Wang Haohao Fu Chuanzheng Zhou Wensheng Cai Xueguang Shao Shu-Lin Liu Dai-Wen Pang State Key Laboratory of Medicinal Chemical biology Frontiers Science Centre for New Organic MatterTianjin Key Laboratory of Biosensing and Molecular Recognition Research Centre for Analytical Sciences College of Chemistry School of Medicine and Frontiers Science Centre for Cell Responses Nankai University Haihe Laboratory of Sustainable Chemical Transformations

The cell nucleus is the main site for the storage and replication of genetic material, and the synthesis of substances in the nucleus is rhythmic, regular and strictly regulated by physiological processes. However,whether exogenous substances, such as nanoparticles, can be synthesized in situ in the nucleus of live cells has not been reported. Here, we have achieved in-situ synthesis of CdSxSe1-xquantum dots（QDs） in the nucleus by regulation of the glutathione（GSH） metabolic pathway. High enrichment of GSH in the nucleus can be accomplished by the addition of GSH with the help of the Bcl-2 protein. Then, high-valence Se is reduced to low-valence Se by glutathione-reductase-catalyzed GSH, and interacts with the Cd precursor formed through Cd and thiol-rich proteins, eventually generating QDs in the nucleus. Our work contributes to a new understanding of the syntheses of substances in the cell nucleus and will pave the way for the development of advanced ‘supercells’.

关键词： glutathione live cell nucleus quantum dot intracellular synthesis

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Identification and functional characterization of fish IL‑17 receptors suggest important roles in the response to nodavirus infection

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Marine Life Science & Technology 2024年第2期6卷 252-265页

作者： Carmen González‑Fernández Miguel A.García‑Álvarez Alberto Cuesta Department of cell biology and Histology Faculty of BiologyUniversity of Murcia30100 MurciaSpain Laboratoire d’écotoxicologie Centre de Lyon-VilleurbanneINRAEUR RiverLy69625 VilleurbanneFrance

Th17 is a lymphocyte T helper(Th)subpopulation relevant in the control and regulation of the immune response characterized by the production of interleukin(IL)-17.This crucial cytokine family acts through their binding to the IL-17 receptors(IL-17R),having up to six members.Although the biology of fish Th17 is well-recognized,the molecular and functional characterization of IL-17 and IL-17R has been limited.Thus,our aim was to identify and characterize the IL-17R repertory and regulation in the two main Mediterranean cultured fish species,the gilthead seabream(Sparus aurata)and the European sea bass(Dicentrarchus labrax).Our in silico results showed the clear identification of six members in each fish species,from IL-17RA to IL-17RE-like,with well-conserved gene structure and protein domains with their human orthologues.All of them showed wide and constitutive transcription in naïve tissues but with highest levels in mucosal tissues,namely skin,gill or intestine.In leucocytes,T mitogens showed the strongest up-regulation in most of the il17 receptors though il17ra resulted in inhibition by most stimulants.Interestingly,in vivo nodavirus infection resulted in alterations on the transcription of il17 receptors.While nodavirus infection led to some increments in the il17ra,il17rb,il17rc and il17rd transcripts in the susceptible European sea bass,many down-regulations were observed in the resistant gilthead seabream.Our data identify the presence and conservation of six coding IL-17R in gilthead seabream and European sea bass as well as their differential regulation in vitro and upon nodavirus infection.

关键词： Th17 cells IL-17 receptors Immunity Teleost fish Nodavirus(NNV) Aquaculture

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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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Research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of molecular cell biology Sungkyunkwan University School of MedicineSuwonKorea Single cell Network Research Center Sungkyunkwan University School of MedicineSuwonKorea Research institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information Research institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative diseases.However,the molecular mechanisms underlying neuromuscular dysfunction are currently unclear.Recent studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle maintenance.In the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using Hb9-Cre.mnKO exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and lethality.Prmt1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve injury.The transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and mitochondria.Consistently,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor neurons.Furthermore,Prmt1 inhibition in motor neurons elicited mitochondrial dysfunction.Our findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle loss.Thus,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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