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Functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure

Journal of genetics and Genomics 2024年第8期51卷 844-854页

作者： Yi Hu Huaming Cao Jie Sheng Yizhuo Sun Yuping Zhu Qin Lin Na Yi Siyu He Luying Peng Li Li State Key laboratory of Cardiology and Medical Innovation Center Shanghai East HospitalTongji University School of MedicineShanghai 200120China Shanghai Arrhythmias Research Center Shanghai East HospitalTongji University School of MedicineShanghai 200120China laboratory of Molecular genetics and Stem cell Differentiation Tongji University School of MedicineShanghai 200120China Department of Cardiology Shanghai Shibei HospitalShanghai 200435China Research Units of Origin and Regulation of Heart Rhythm Chinese Academy of Medical SciencesShanghai 200120China

Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure,with noncoding RNAs exerting regulatory ***,the molecular function of circular RNAs(circRNAs)in the progression from cardiac hypertrophy to heart failure remains *** uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure,we construct a global triple network(microRNA,circRNA,and mRNA)based on the competitive endogenous RNA(ceRNA)*** observe that cardiac hypertrophy-related circRNA(circRNA CHRC),within the ceRNA network,is down-regulated in both transverse aortic constriction mice and Ang-II--treated primary mouse *** circRNA CHRC increases cross-sectional cell area,atrial natriuretic peptide,andβ-myosin heavy chain levels in primary mouse *** screening shows that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in *** with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p,while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC *** summary,circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.

关键词： circRNA CHRC Heart failure CeRNA miR-431-4p KIf15

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Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation

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Science China(Life Sciences) 2024年第5期67卷 1035-1050页

作者： Yaling Wang Jingwen Chen Xueying Huang Bangguo Wu Peng Dai Feng Zhang Jinsong Li Lingbo Wang State Key laboratory of Genetic Engineering Shanghai Key Laboratory of Metabolic Remodeling and HealthInstitute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China NHC Key Lab of Reproduction Regulation(Shanghai Institute for Biomedical and Pharmaceutical Technologies) School of PharmacyFudan UniversityShanghai 200433China Shanghai Key laboratoryof Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchoolof Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key laboratory of cell Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

Cytosine base editing achieves C·G-to-T·A substitutions and can convert four codons(CAA/CAG/CGA/TGG)into STOP-codons(induction of STOP-codons,iSTOP)to knock out genes with reduced *** enables direct phenotyping in founders’somatic cells,but it remains unknown whether this works in founders’germ cells so as to rapidly reveal novel genes for ***,we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders’germ cells:Cfap43-iSTOP male founders manifest expected sperm features resembling human“multiple morphological abnormalities of the flagella”syndrome(i.e.,MMAF-like features),while oocytes of Zp3-iSTOP female founders have no zona *** further illustrate iSTOP’s utility for dissecting the functions of unknown genes with Ccdc183,observing MMAF-like features and male infertility in Ccdc183-iSTOP founders,phenotypes concordant with those of Ccdc183-KO *** ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar *** study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation,and rapidly reveals the essentiality of Ccdc183 in fertility,thus providing a time-saving approach for validating genetic defects(like nonsense mutations)for human infertility.

关键词： disease modeling infertility multiple morphological abnormalities of the flagella(MMAF) induction of STOP-codons(iSTOP CRISPR-STOP) sperm motility

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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

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Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of genetics and Medicine TIGEMPozzuoliNaples 80131Italy Medical genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy Department of Molecular and human genetics Baylor College of MedicineHoustonTX 77030USA Department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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Combining QTL Mapping and Multi-Omics Identify Candidate Genes for Nutritional Quality Traits during Grain Filling Stage in Maize

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Phyton-International Journal of Experimental Botany 2024年第7期93卷 1441-1453页

作者： Pengcheng Li Tianze Zhu Yunyun Wang Shuangyi Yin Xinjie Zhu Minggang Ji Wenye Rui Houmiao Wang Zefeng Yang Chenwu Xu Jiangsu Key laboratory of Crop genetics and Physiology Key Laboratory of Plant Functional Genomics of the Ministry of EducationJiangsu Key Laboratory of Crop Genomics and Molecular BreedingAgricultural College of Yangzhou UniversityYangzhou225009China Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops Yangzhou UniversityYangzhou225009China

The nutritional composition and overall quality of maize kernels are largely determined by the key chemical com-ponents:protein,oil,and ***,the genetic basis underlying these nutritional quality traits during grainﬁlling remains poorly *** this study,the concentrations of protein,oil,and starch were studied in 204 recombinant inbred lines resulting from a cross between DH1M and T877 at four different stages *** the traits exhibited considerable phenotypic *** the grain-ﬁlling stage,the levels of protein and starch content generally increased,whereas oil content decreased,with signiﬁcant changes observed between 30 and 40 days after *** trait locus(QTL)mapping was conducted and a total of 32 QTLs,comprising 14,12,and 6 QTLs for grain protein,oil,and starch content were detected,*** QTLs were consistently detectable across different time *** integrating QTL analysis,glo-bal gene expression proﬁling,and comparative genomics,we identiﬁed 157,86,and 54 differentially expressed genes harboring nonsynonymous substitutions between the parental lines for grain protein,oil,and starch con-tent,*** gene function annotation prioritized 15 candidate genes potentially involved in reg-ulating grain quality traits,including those encoding transcription factors(NAC,MADS-box,bZIP,and MYB),cell wall invertase,cellulose-synthase-like protein,cell division cycle protein,trehalase,auxin-responsive factor,and phloem protein *** study offers signiﬁcant insights into the genetic architecture of maize kernel nutritional quality and identiﬁes promising QTLs and candidate genes,which are crucial for the genetic enhance-ment of these traits in maize breeding programs.

关键词： Maize protein oil starch QTL mapping candidate genes

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Promoting the production of challenging proteins via induced expression in CHO cells and modified cell-free lysates harboring T7 RNA polymerase and mutant eIF2α

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Synthetic and Systems Biotechnology 2024年第3期9卷 416-424页

作者： Jeffrey L.Schloßhauer Lena Tholen Alexander Korner Stefan Kubick Sofia Chatzopoulou Anja Honow Anne Zemella Fraunhofer Project Group PZ-Syn of the Fraunhofer Institute for cell therapy and Immunology-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Fraunhofer Institute for cell therapy and Immunology-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Faculty of Health Sciences Joint Faculty of the Brandenburg University of Technology Cottbus-SenftenbergThe Brandenburg Medical School Theodor FontaneUniversity of PotsdamPotsdamGermany Institute for Chemistry and Biochemistry Laboratory of Protein BiochemistryFreie Universitat BerlinThielallee 6314195BerlinGermany Institute of Biotechnology Technische Universit¨at BerlinStraße des 17.Juni 13510623BerlinGermany New/era/mabs GmbH August-Bebel-Str.8914482PotsdamGermany

Chinese hamster ovary(CHO)cells are crucial in biopharmaceutical production due to their scalability and capacity for human-like post-translational ***,toxic proteins and membrane proteins are often difficult-to-express in living ***,cell-free protein synthesis can be *** study explores innovative strategies for enhancing the production of challenging proteins through the modification of CHO cells by investigating both,cell-based and cell-free approaches.A major result in our study involves the integration of a mutant eIF2 translation initiation factor and T7 RNA polymerase into CHO cell lysates for cell-free protein *** resulted in elevated yields,while eliminating the necessity for exogenous additions during cell-free production,thereby substantially enhancing ***,we explore the potential of the Rosa26 genomic site for the integration of T7 RNA polymerase and cell-based tetracycline-controlled protein *** findings provide promising advancements in bioproduction technologies,offering flexibility to switch between cell-free and cell-based protein production as needed.

关键词： Inducible expression CHO cells cell-free protein synthesis CRISPR T7 RNA polymerase eIF2 Rosa26

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A cell transcriptomic profile p ovides insights into adipocytes of porcine mammary gland across development

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Journal of Animal Science and Biotechnology 2024年第1期15卷 182-200页

作者： Yongliang Fan Long Jin Zhiping He Tiantian Wei Tingting Luo Jiaman Zhang Can Liu Changjiu Dai Chao A Yan Liang Xuan Tao Xuebin Lv Yiren Gu Mingzhou Li State Key laboratory of Swine and Poultry Breeding Industry College of Animal Science and TechnologySichuan Agricultural UniversityChengdu 611130China Key laboratory of Qinghai‑Tibetan Plateau Animal Genetic Resource Reservation and Utilization Southwest Minzu UniversityChengdu 610041China Animal Breeding and genetics Key laboratory of Sichuan Province Sichuan Animal Science AcademyChengdu 610000China

Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring *** Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages(d 90 of gestation, G90;d 0 after lactation, L0;d 20 after lactation, L20;2 d post natural involution, PI2;7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation(G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation(L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution(PI2 and PI7), epithelial cell populatio

关键词： Adipocytes cell–cell interaction Development Mammary gland snRNA-seq

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The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development

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Journal of Molecular cell Biology 2024年第1期16卷 43-53页

作者： Xiaozhen Song Ruixing Hu Yi Chen Man Xiao Hong Zhang Shengnan Wu Qing Lu Molecular Diagnostic laboratory Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200040China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China laboratory of Development and Diseases and State Key laboratory for Medical Genomics Shanghai Institute of HematologyRuĳin HospitalShanghai JiaoTong University School of MedicineShanghai 200025China

TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways,contributing to immune responses,tumor progression,and embryonic *** mutations within the coiled-coil(CC)domain and WD40 repeat domain of TRAF7 could cause brain tumors,while germline pathogenic mutations contribute to severe developmental ***,the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains *** this study,we employed zebrafish as an in vivo model ***7 knock down caused defects in zebrafish embryonic *** determined the crystal structure of TRAF7 CC domain at 3.3Åresolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic ***,disease-causing mutations in TRAF7 CC region could impair the trimer formation,consequently impacting early embryonic development of ***,our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.

关键词： TRAF7 coiled-coil domain crystal structure trimerization embryonic development

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The VAMP-associated protein VAP27-1 plays a crucial role in plant resistance to ER stress by modulating ER–PM contact architecture in Arabidopsis

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Plant Communications 2024年第7期5卷 261-279页

作者： Yi Man Yue Zhang Linghui Chen Junhui Zhou Yufen Bu Xi Zhang Xiaojuan Li Yun Li Yanping Jing Jinxing Lin National Engineering Research Center of Tree Breeding and Ecological Restoration College of Biological Sciences and TechnologyBeijing Forestry UniversityBeijing 100083China Key laboratory of genetics and Breeding in Fore These authors contributed equally to this article

The endoplasmic reticulum(ER)and the plasma membrane(PM)form ER–PM contact sites(EPCSs)that allow the ER and PM to exchange materials and ***-induced disruption of protein folding triggers ER stress,and the cell initiates the unfolded protein response(UPR)to resist the ***,whether EPCSs play a role in ER stress in plants remains ***-ASSOCIATED MEMBRANE PROTEIN(VAMP)-ASSOCIATED PROTEIN 27-1(VAP27-1)functions in EPCS tethering and is encoded by a family of 10 genes(VAP27-1–10)in Arabidopsis ***,we used CRISPR-Cas9-mediated genome editing to obtain a homozygous vap27-1 vap27-3 vap27-4(vap27-1/3/4)triple mutant lacking three of the key VAP27 family members in *** vap27-1/3/4 mutant exhibits defects in ER–PM connectivity and EPCS architecture,as well as excessive UPR *** further showed that relocation of VAP27-1 to the PM mediates specific VAP27-1-related EPCS remodeling and expansion under ER ***,the spatiotemporal dynamics of VAP27-1 at the PM increase ER–PM connectivity and enhance Arabidopsis resistance to ER *** addition,we revealed an important role for intracellular calcium homeostasis in the regulation of UPR *** together,these results broaden our understanding of the molecular and cellular mechanisms of ER stress and UPR signaling in plants,providing additional clues for improving plant broad-spectrum resistance to different stresses.

关键词： Arabidopsis VAP27-1 ER–PM contact sites ER stress unfolded protein response

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Hepatic HDAC3 Regulates Systemic Iron Homeostasis and Ferroptosis via the Hippo Signaling Pathway

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Research 2024年第3期2023卷 499-511页

作者： Hongen Meng Yingying Yu Enjun Xie Qian Wu Xiangju Yin Bin Zhao Junxia Min Fudi Wang The Second Afiliated Hospital The First Affiliated HospitalInstitute of Translational MedicineScho of Public HealthZhejiang University School of MedicineHangzhouChina institute of Emergency Management Henan Polytechnic UniversityJiaozuoChina MOE Key laboratory of Biosystems Homeostasis and Protection Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biologyand Innovation Center for Cell Signaling NetworkLife Sciences InstituteZhejiang UniversityHangzhou 310058China.

Histone deacetylases(HDACs)are epigenetic regulators that play an important role in determining cell fate and maintaining cellular ***,whether and how HDACs regulate iron metabolism and ferroptosis(an iron-dependent form of cell death)remain ***,the putative role of hepatic HDACs in regulating iron metabolism and ferroptosis was investigated using genetic mouse *** lacking Hdac3 expression in the liver(Hdac3-LKO mice)have significantly reduced hepatic Hamp mRNA(encoding the peptide hormone hepcidin)and altered iron *** profiling of Hdac3-LKO mice suggests that the Hippo signaling pathway may be downstream of ***,using a Hippo pathway inhibitor and overexpressing the transcriptional regulator Yap(Yes-associated protein)significantly reduced Hamp mRNA *** a promoter reporter assay,we then identified 2 Yap-binding repressor sites within the human HAMP promoter *** also found that inhibiting Hdac3 led to increased translocation of Yap to the nucleus,suggesting activation of ***,knock-in mice expressing a constitutively active form of Yap(Yap K342M)phenocopied the altered hepcidin levels observed in Hdac3-LKO ***,we show that iron-overload-induced ferroptosis underlies the liver injury that develops in Hdac3-LKO mice,and knocking down Yap expression in Hdac3-LKO mice reduces both iron-overload-and ferroptosis-induced liver *** results provide compelling evidence supporting the notion that HDAC3 regulates iron homeostasis via the Hippo/Yap pathway and may serve as a target for reducing ferroptosis in iron-overload-related diseases.

关键词： homeostasis metabolism expressing

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Spirotetramat reduces fitness of the spotted-wing Drosophila,Drosophila suzukii

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Insect Science 2024年第4期31卷 1222-1230页

作者： Jing Yang Justin Flaven-Pouchon Yiwen Wang Bernard Moussian Section of Animal genetics Interfaculty Institute of Cell BiologyUniversity of TübingenTübingenGermany School of Pharmaceutical Science and Technology Tianjin UniversityTianjinChina INRAE CNRSUniversitéCôte d'AzurInstitut Sophia AgrobiotechSophia AntipolisFrance

With climate change,the spotted-wing Drosophila(SWD,Drosophila suzukii)invades a great number of fruit production regions worldwide.A plethora of insecticides are being applied for management of this *** expected,SWD develops resistance against some potent insecticides or is rather insensitive to some ***,there is an urgent need to identify and characterize alternative insecticides to control SWD ***,we have studied the effects of the orally applied inhibitor of the fatty acid synthesis pathway spirotetramat on SWD fitness with respect to fecundity and surface barrier function at different *** our experiments,we applied spirotetramat mixed with baker's yeast and showed that females and males were not repelled by effective concentrations of this *** found that spirotetramat,by trend,lowers egg numbers laid by fed *** eggs rapidly desiccate,and only a few larvae *** is lethal to larvae and reduces survival of adult flies under low-humidity *** together,based on our data,we propose to use yeast supplemented with spirotetramat and additional SWD-specific attractants in traps in non-crop areas in order to eradicate SWD populations before they infest crop production sites.

关键词： desiccation Drosophila suzuki insecticide lipids

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