查看更多>>摘要:Heterosis,also known as hybrid vigor,is commonly observed in rice crosses.The hybridization of rice species or subspecies exhibits robust hybrid vigor,however,the direct harnessing of this vigor is hindered by reproductive isolation.Here,we review recent advances in the understanding of the molecular mech-anisms governing reproductive isolation in inter-subspecific and inter-specific hybrids.This review en-compasses the genetic model of reproductive isolation within and among Oryza sativa species,emphasizing the essential role of mitochondria in this process.Additionally,we delve into the molecular intricacies governing the interaction between mitochondria and autophagosomes,elucidating their signif-icant contribution to reproductive isolation.Furthermore,our exploration extends to comprehending the evolutionary dynamics of reproductive isolation and speciation in rice.Building on these advances,we offer a forward-looking perspective on how to overcome the challenges of reproductive isolation and facilitate the utilization of heterosis in future hybrid rice breeding endeavors.
查看更多>>摘要:The post-transcriptional regulation of mRNA is a crucial component of gene expression.The disruption of this process has detrimental effects on the normal development and gives rise to various diseases.Searching for novel post-transcriptional regulators and exploring their roles are essential for understanding development and disease.Through a multimodal analysis of red blood cell trait genome-wide association studies(GWAS)and transcriptomes of erythropoiesis,we identify FAM46C,a non-canonical RNA poly(A)polymerase,as a necessary factor for proper red blood cell development.FAM46C is highly expressed in the late stages of the erythroid lineage,and its developmental upregulation is controlled by an erythroid-specific enhancer.We demonstrate that FAM46C stabilizes mRNA and regulates erythroid differentiation in a polymerase activity-dependent manner.Furthermore,we identify transcripts of lysosome and mito-chondria components as highly confident in vivo targets of FAM46C,which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox homeostasis.In conclusion,our study unveils a unique role of FAM46C in positively regulating lysosome and mitochondria components,thereby promoting erythropoiesis.
查看更多>>摘要:Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection often leads to pulmonary com-plications.Cardiovascular sequelae,including myocarditis and heart failure,have also been reported.Here,the study presents two fulminant myocarditis cases infected by SARS-CoV-2 exhibiting remarkable elevation of cardiac biomarkers without significant pulmonary injury,as determined by imaging examina-tions.Immunohistochemical staining reveals the viral antigen within cardiomyocytes,indicating that SARS-CoV-2 could directly infect the myocardium.The full viral genomes from respiratory,anal,and myocardial specimens are obtained via next-generation sequencing.Phylogenetic analyses of the whole genome and spike gene indicate that viruses in the myocardium/pericardial effusion and anal swabs are closely related and cluster together yet diverge from those in the respiratory samples.In addition,unique mutations are found in the anal/myocardial strains compared to the respiratory strains,suggesting tissue-specific virus mutation and adaptation.These findings indicate genetically distinct SARS-CoV-2 variants have infiltrated and disseminated within myocardial tissues,independent of pulmonary injury,and point to different infection routes between the myocardium and respiratory tract,with myocardial infections potentially arising from intestinal infection.These findings highlight the potential for systemic SARS-CoV-2 infection and the importance of a thorough multi-organ assessment in patients for a comprehensive understanding of the pathogenesis of COVID-19.
查看更多>>摘要:Endometriosis refers to as an estrogen-dependent disease.Estrogen receptor β(ERβ),the main estrogen receptor subtype which is encoded by the estrogen receptor 2(ESR2)gene,can mediate the action of estrogen in endometriosis.Although selective estrogen receptor modulators can target the ERβ,they are not specific due to the wide distribution of ERβ.Recently,long noncoding RNAs have been implicated in endometriosis.Therefore,we aim to explore and validate the downstream regulatory mechanism of ERβ,and to investigate the potential role of long intergenic noncoding RNA 1018(LINC01018)as a nonhormonal treatment for endometriosis.Our study demonstrates that the expression levels of ESR2 and LINC01018 are increased in ectopic endometrial tissues and reveals a significant positive correlation between the ESR2 and LINC01018 expression.Mechanistically,ERβ directly binds to an estrogen response element located in the LINC01018 promoter region and activates LINC01018 transcription.Functionally,ERβ can regulate the CDC25C/CDK1/CyclinB1 pathway and promote ectopic endometrial stromal cell proliferation via LINC01018 in vitro.Consistent with these findings,the knockdown of LINC01018 inhibits endometriotic lesion proliferation in vivo.In summary,our study demonstrates that the ERβ/LINC01018/CDC25C/CDK1/CyclinB1 signaling axis regulates endometriosis progression.
查看更多>>摘要:Clathrin-mediated endocytosis has been implicated in various physiological processes,including nutrient uptake,signal transduction,synaptic vesicle recycling,maintenance of cell polarity,and antigen presen-tation.Despite prior knowledge of its importance as a key regulator in promoting clathrin-mediated endocytosis,the physiological function of α-and y-adaptin binding protein(aagab)remains elusive.In this study,we investigate the biological function of aagab during zebrafish development.We establish a loss-of-function mutant of aagab in zebrafish,revealing impaired swimming and early larval mortality.Given the high expression level of aagab in the brain,we probe into its physiological role in the nervous system.aagab mutants display subdued calcium responses and local field potential in the optic tectal neurons,aligning with reduced neurotransmitter release(e.g.,norepinephrine)in the tectal neuropil of aagab mutants.Overexpressing aagab mRNA or nervous stimulant treatment in mutants restores neurotransmitter release,calcium responses,swimming ability,and survival.Furthermore,our observations show delayed release of FM 1-43 in AAGAB knockdown differentiated neuroblastoma cells,pointing towards a probable link to defective clathrin-mediated synaptic vesicle recycling.In conclusion,our study underscores the signifi-cance of Aagab in neurobiology and suggests its potential impacts on neurological disorders.
查看更多>>摘要:Identical-by-descent(IBD)is a fundamental genomic characteristic in population genetics and has been widely used for population history reconstruction.However,limited by the nature of IBD,which could only capture the relationship between two individuals/haplotypes,existing IBD-based history inference is con-strained to two populations.In this study,we propose a framework by leveraging IBD sharing in multi-population and develop a method,MatrixIBD,to reconstruct recent multi-population migration history.Specifically,we employ the structured coalescent theory to precisely model the genealogical process and then estimate the IBD sharing across multiple populations.Within our model,we establish a theoretical connection between migration history and IBD sharing.Our method is rigorously evaluated through sim-ulations,revealing its remarkable accuracy and robustness.Furthermore,we apply MatrixIBD to Central and South Asia in the Human Genome Diversity Project and successfully reconstruct the recent migration history of three closely related populations in South Asia.By taking into account the IBD sharing across multiple populations simultaneously,MatrixIBD enables us to attain clearer and more comprehensive in-sights into the history of regions characterized by complex migration dynamics,providing a holistic perspective on intricate patterns embedded within the recent population migration history.
查看更多>>摘要:A 5'-leader,known initially as the 5'-untranslated region,contains multiple isoforms due to alternative splicing(aS)and alternative transcription start site(aTSS).Therefore,a representative 5'-leader is demanded to examine the embedded RNA regulatory elements in controlling translation efficiency.Here,we develop a ranking algorithm and a deep-learning model to annotate representative 5'-leaders for five plant species.We rank the intra-sample and inter-sample frequency of aS-mediated transcript isoforms using the Kruskal-Wallis test-based algorithm and identify the representative aS-5'-leader.To further assign a representative 5'-end,we train the deep-learning model 5'IeaderP to learn aTSS-mediated 5'-end distribution patterns from cap-analysis gene expression data.The model accurately predicts the 5'-end,confirmed experimentally in Arabidopsis and rice.The representative 5'-leader-contained gene models and 5'leaderP can be accessed at RNAirport(http://www.rnairport.com/leader5P/).The Stage 1 annotation of 5'-leader records 5'-leader diversity and will pave the way to Ribo-Seq open-reading frame annotation,identical to the project recently initiated by human GENCODE.