Recessive resistance mediated by mutations in the eukaryotic translation initiation factor 4E(eIF4E),has proven effective against diverse potyviruses and is extensively utilized in breeding programs.However,the rise o...Recessive resistance mediated by mutations in the eukaryotic translation initiation factor 4E(eIF4E),has proven effective against diverse potyviruses and is extensively utilized in breeding programs.However,the rise of resistance-breaking(RB)strains and emerging potyviral species necessitates the development of more durable and broad-spectrum resistance strategies.In this study,our field survey in Yunnan,China,identified potato virus Y(PVY)RB isolates,as well as the prevalence of tobacco vein banding mosaic virus(TVBMV)and chilli veinal mottle virus(ChiVMV),in tobacco carrying the recessive va locus,which lacks the eIF4E1-S susceptibility gene,due to a chromosomal deletion.Protein interaction and viral infection assays demonstrated that both eIF4E1-S and eIFiso4E-T are used by PVY RB as susceptibility factors for infection,with the combined inactivation of these genes confering durable resistance.Similarly,the knockout of eIFiso4E-S,in the va genetic background,provided effective resistance to TVBMV and reduced susceptibility to ChiVMV.Notably,pyramiding mutations in eIFiso4E-S and eIFiso4E-T,in va tobacco,generated plants exhibiting robust,broad-spectrum resistance,to all three viruses,without compromising plant development.These findings underscore the potential of stacking eIF4E mutations to engineer durable,broad-spectrum resistance to potyviruses in tobacco,offering a promising strategy for crop improvement.展开更多
The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatm...The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].展开更多
Turnip mosaic virus(TuMV)constitutes one of the primary diseases affecting Brassica rapa,severely impacting its production and resulting in crop failures in various regions worldwide.Recent research has demonstrated t...Turnip mosaic virus(TuMV)constitutes one of the primary diseases affecting Brassica rapa,severely impacting its production and resulting in crop failures in various regions worldwide.Recent research has demonstrated the significance of plant translation initiation factors,specifically the eIF4E and eIF4G family genes,as essential recessive disease resistance genes.In our study,we conducted evolutionary and gene expression studies,leading us to identify e IF(iso)4E.c as a potential TuMV-resistant gene.Leveraging CRISPR/Cas9 technology,we obtained mutant B.rapa plants with edited eIF(iso)4E.c gene.We confirmed eIF(iso)4E.c confers resistance against TuMV through phenotypic observations and virus content evaluations.Furthermore,we employed ribosome profiling assays on eif(iso)4e.c mutant seedlings to unravel the translation landscape in response to TuMV.Interestingly,we observed a moderate correlation between the fold changes in gene expression at the transcriptional and translational levels(R^(2)=0.729).Comparative analysis of ribosome profiling and RNA-seq data revealed that plant-pathogen interaction,and MAPK signaling pathway-plant pathways were involved in eIF(iso)4E.c-mediated TuMV resistance.Further analysis revealed that sequence features,coding sequence length,and normalized minimal free energy,influenced the translation efficiency of genes.Our study highlights that the loss of e IF(iso)4E.c can result in a highly intricate translation mechanism,acting synergistically with transcription to confer resistance against TuMV.展开更多
基金supported by National Natural Science Foundation of China(31860490)YNTC funds(2023530000241007 and 2017YN02)+1 种基金Yunnan Daguan Lab(YNDG202302ZY01)CLZ is supported by the Postdoctoral Fellowship Program of CPSF under grant number GZC20241527。
文摘Recessive resistance mediated by mutations in the eukaryotic translation initiation factor 4E(eIF4E),has proven effective against diverse potyviruses and is extensively utilized in breeding programs.However,the rise of resistance-breaking(RB)strains and emerging potyviral species necessitates the development of more durable and broad-spectrum resistance strategies.In this study,our field survey in Yunnan,China,identified potato virus Y(PVY)RB isolates,as well as the prevalence of tobacco vein banding mosaic virus(TVBMV)and chilli veinal mottle virus(ChiVMV),in tobacco carrying the recessive va locus,which lacks the eIF4E1-S susceptibility gene,due to a chromosomal deletion.Protein interaction and viral infection assays demonstrated that both eIF4E1-S and eIFiso4E-T are used by PVY RB as susceptibility factors for infection,with the combined inactivation of these genes confering durable resistance.Similarly,the knockout of eIFiso4E-S,in the va genetic background,provided effective resistance to TVBMV and reduced susceptibility to ChiVMV.Notably,pyramiding mutations in eIFiso4E-S and eIFiso4E-T,in va tobacco,generated plants exhibiting robust,broad-spectrum resistance,to all three viruses,without compromising plant development.These findings underscore the potential of stacking eIF4E mutations to engineer durable,broad-spectrum resistance to potyviruses in tobacco,offering a promising strategy for crop improvement.
基金funded by the National Natural Science Foundation of China(Grant Nos.:82004081 and 52073145)the National Natural Science Foundation of Nanjing University of Chinese Medicine,China(Grant No.:NZY82004081).
文摘The treatment of non-small cell lung cancer(NSCLC)remains a challenge due to tumor evolution during anti-angiogenesis therapies,in which the mechanism of vascular mimicry(VM)is believed to result in ineffective treatment[1].To conquer this challenge,substantial effort has recently been devoted to seeking out natural compounds on account of their multitarget actions.As a traditional herbal medicine,platycodin D(PD)is the major bioactive monomer derived from Platycodon grandiflorum(P.grandiflorum)and is used as an expectorant for pulmonary disease in Asia[2].
基金supported by grants from the Scientist Training Program of BAAFS (Grant No.JKZX202406)the Innovation and Capacity-Building Project of BAAFS (Grant No.KJCX20230221)+2 种基金Collaborative innovation program of the Beijing Vegetable Research Center (Grant No.XTCX202302)the National Natural Science Foundation of China (Grant No.32072567)the China Agriculture Research System of MOF and MARA (Grant No.CARS-A03)。
文摘Turnip mosaic virus(TuMV)constitutes one of the primary diseases affecting Brassica rapa,severely impacting its production and resulting in crop failures in various regions worldwide.Recent research has demonstrated the significance of plant translation initiation factors,specifically the eIF4E and eIF4G family genes,as essential recessive disease resistance genes.In our study,we conducted evolutionary and gene expression studies,leading us to identify e IF(iso)4E.c as a potential TuMV-resistant gene.Leveraging CRISPR/Cas9 technology,we obtained mutant B.rapa plants with edited eIF(iso)4E.c gene.We confirmed eIF(iso)4E.c confers resistance against TuMV through phenotypic observations and virus content evaluations.Furthermore,we employed ribosome profiling assays on eif(iso)4e.c mutant seedlings to unravel the translation landscape in response to TuMV.Interestingly,we observed a moderate correlation between the fold changes in gene expression at the transcriptional and translational levels(R^(2)=0.729).Comparative analysis of ribosome profiling and RNA-seq data revealed that plant-pathogen interaction,and MAPK signaling pathway-plant pathways were involved in eIF(iso)4E.c-mediated TuMV resistance.Further analysis revealed that sequence features,coding sequence length,and normalized minimal free energy,influenced the translation efficiency of genes.Our study highlights that the loss of e IF(iso)4E.c can result in a highly intricate translation mechanism,acting synergistically with transcription to confer resistance against TuMV.
