Plant intracellular nucleotide-binding domain leucine-rich repeat(NLR)receptors play crucial roles in immune responses against pathogens.How diverse NLRs recognize different pathogen effectors remains a significant qu...Plant intracellular nucleotide-binding domain leucine-rich repeat(NLR)receptors play crucial roles in immune responses against pathogens.How diverse NLRs recognize different pathogen effectors remains a significant ques-tion.A recent study published in Nature uncovered how pepper NLR Tsw detects phytohormone receptors’interfer-ence caused by tomato spotted wilt virus(TSWV)effector,triggering a robust immune response,showcasing a new manner of NLR guarding.展开更多
N-Hydroxypipecolic acid(NHP)is a signaling molecule crucial for systemic acquired resistance(SAR),a systemic immune response in plants that provides long-lasting and broad-spectrum protection against secondary pathoge...N-Hydroxypipecolic acid(NHP)is a signaling molecule crucial for systemic acquired resistance(SAR),a systemic immune response in plants that provides long-lasting and broad-spectrum protection against secondary pathogen infections.To identify negative regulators of NHP biosynthesis,we performed a forward genetic screen to search for mutants with elevated expression of the NHP biosynthesis gene FLAVIN-DEPENDENT MONOOXYGENASE 1(FMO1).Analysis of two constitutive expression of FMO1(cef)and one induced expression of FMO1(ief)mutants revealed that the AIPP3–PHD2–CPL2 protein complex,which is involved in the recognition of the histone modification H3K27me3 and transcriptional repression,contributes to the negative regulation of FMO1 expression and NHP biosynthesis.Our study suggests that epigenetic regulation plays a crucial role in controlling FMO1 expression and NHP levels in plants.展开更多
Undruggable proteins are a class of proteins that are often characterized by large,complex structures or functions that are diffcult to interfere with using conventional drug design strategies.Targeting such undruggab...Undruggable proteins are a class of proteins that are often characterized by large,complex structures or functions that are diffcult to interfere with using conventional drug design strategies.Targeting such undruggable targets has been considered also a great opportunity for treatment of human diseases and has attracted substantial efforts in the field of medicine.Therefore,in this review,we focus on the recent development of drug discovery targeting"undruggable"proteins and their application in clinic.To make this review well organized,we discuss the design strategies targeting the undruggable proteins,including covalent regulation,allosteric inhibition,protein-protein/DNA interaction inhibition,targeted proteins regulation,nucleic acid-based approach,immunotherapy and others.展开更多
Defense-related terpenoid biosynthesis in conifers is a dynamic process closely associated with specialized anatomical structures that allows conifers to cope with attack from many potential pests and pathogens. The c...Defense-related terpenoid biosynthesis in conifers is a dynamic process closely associated with specialized anatomical structures that allows conifers to cope with attack from many potential pests and pathogens. The constitutive and inducible terpenoid defense of conifers involves several hundred different monoterpenes, sesquiterpenes and diterpenes. Changing arrays of these many compounds are formed from the general isoprenoid pathway by activities of large gene families for two classes of enzymes, the terpene synthases and the cytochrome P450-dependent monooxygenases of the CYP720B group. Extensive studies have been conducted on the genomics, proteomics and molecular biochemical characterization of these enzymes. Many of the conifer terpene synthases are multi-product enzymes, and the P450 enzymes of the CYP720B group are promiscuous in catalyzing multiple oxidations, along homologous series of diterpenoids, from a broad spectrum of substrates. The terpene synthases and CYP720B genes respond to authentic or simulated insect attack with increased transcript levels, protein abundance and enzyme activity. The constitutive and induced oleoresin terpenoids for conifer defense accumulate in preformed cortical resin ducts and in xylem trauma-associated resin ducts. Formation of these resin ducts de novo in the cambium zone and developing xylem, following insect attack or treatment of trees with methyl jasmonate, is a unique feature of the induced defense of long-lived conifer trees.展开更多
Salicylic acid(SA)has long been known to be essential for basal defense and systemic acquired resistance(SAR).N-Hydroxypipecolic acid(NHP),a recently discovered plant metabolite,also plays a key role in SAR and to a l...Salicylic acid(SA)has long been known to be essential for basal defense and systemic acquired resistance(SAR).N-Hydroxypipecolic acid(NHP),a recently discovered plant metabolite,also plays a key role in SAR and to a lesser extent in basal resistance.Following pathogen infection,levels of both compounds are dramatically increased.Analysis of SA-or SAR-deficient mutants has uncovered how SA and NHP are biosynthesized.The completion of the SA and NHP biosynthetic pathways in Arabidopsis allowed better understanding of how they are regulated.In this review,we discuss recent progress on SA and NHP biosynthesis and their regulation in plant immunity.展开更多
Two signal molecules, salicylic acid (SA) and N-hydroxypipecolic acid (NHP), play critical roles in plant immunity. The biosynthetic genes of both compounds are positively regulated by master immune-regulating transcr...Two signal molecules, salicylic acid (SA) and N-hydroxypipecolic acid (NHP), play critical roles in plant immunity. The biosynthetic genes of both compounds are positively regulated by master immune-regulating transcription factors SARD1 and CBP60g. However, the relationship between the SA and NHP pathways is unclear. CALMODULIN-BINDING TRANSCRIPTION FACTOR 1 (CAMTA1), CAMTA2, and CAMTA3 are known redundant negative regulators of plant immunity, but the underlying mechanism also remains largely unknown. In this study, through chromatin immunoprecipitation and electrophoretic mobility shift assays, we uncovered that CBP60g is a direct target of CAMTA3, which also negatively regulates the expression of SARD1, presumably via an indirect effect. The autoimmunity of camta3-1 is suppressed by sard1 cbp60g double mutant as well as ald1 and fmo1, two single mutants defective in NHP biosynthesis. Interestingly, a suppressor screen conducted in the camta1/ 2/ 3 triple mutant background yielded various mutants blocking biosynthesis or signaling of either SA or NHP, leading to nearly complete suppression of the extreme autoimmunity of camta1/ 2/ 3, suggesting that the SA and NHP pathways can mutually amplify each other. Together, these results reveal that CAMTAs repress the biosynthesis of SA and NHP by modulating the expression of SARD1 and CBP60g, and that the SA and NHP pathways are coordinated to optimize plant immune response.展开更多
Summary Salicylic acid (SA) is an essential defence hormone in plants. Upon pathogen infection, induced biosynthesis of SA is mediated by Isochorismate synthase 1 (ICS1), whose gene transcription is controlled mai...Summary Salicylic acid (SA) is an essential defence hormone in plants. Upon pathogen infection, induced biosynthesis of SA is mediated by Isochorismate synthase 1 (ICS1), whose gene transcription is controlled mainly through two redundant transcription factors, SAR Deficient 1 (SARD0 and Calmodulin- binding protein 6o-like g (CBP60g).展开更多
Arabidopsis SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1(SARD1)and CALMODULIN-BINDING PROTEIN 60g(CBP60g)are two master transcription factors that regulate many defense-related genes in plant immunity.They are required fo...Arabidopsis SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1(SARD1)and CALMODULIN-BINDING PROTEIN 60g(CBP60g)are two master transcription factors that regulate many defense-related genes in plant immunity.They are required for immunity downstream of the receptor-like protein SUPPRESSOR OF NPR1-1,CONSTITUTIVE 2(SNC2).Constitutive defense responses in the gain-of-function autoimmune snc2-1D mutant are modestly affected in either sard1 or cbp60g single mutants but completely suppressed in the sard1 cbp60g double mutant.Here we report that CBP60b,another member of the CBP60 family,also functions as a positive regulator of SNC2-mediated immunity.Loss-of-function mutations of CBP60b suppress the constitutive expression of SARD1 and enhanced disease resistance in cbp60g-1 snc2-1D,whereas overexpression of CBP60b leads to elevated SARD1 expression and constitutive defense responses.In addition,transient expression of CBP60b in Nicotiana benthamiana activates the expression of the pSARD1::luciferase reporter gene.Chromatin immunoprecipitation assays further showed that CBP60b is recruited to the promoter region of SARD1,suggesting that it directly regulates SARD1 expression.Interestingly,knocking out CBP60b in the wild-type background leads to ENHANCED DISEASE SUSCEPTIBILITY 1(EDS1)-dependent autoimmunity,suggesting that CBP60b is required for the expression of a guardee/decoy or a negative regulator of immunity mediated by receptors carrying an N-terminal Toll-interleukin-1 receptor-like domain.展开更多
The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across ...The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across vertebrate evolution.Moreover,cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors.This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets.We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions.The systematic delineation of SC organization,cell types,and neural connections is further put into context across species as these depend upon laminar architecture.Moreover,we focus on SC neural circuitry involving saccadic eye movement,and cognitive and innate behaviors.Overall,the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.展开更多
Higher plants utilize a variety of immune receptors to recognize pathogens and trigger defense responses.Intracellular nucleotidebinding leucine-rich repeat receptors(NLRs)are widely used for detecting pathogen effect...Higher plants utilize a variety of immune receptors to recognize pathogens and trigger defense responses.Intracellular nucleotidebinding leucine-rich repeat receptors(NLRs)are widely used for detecting pathogen effectors(Jones et al.,2016;Zhou and Zhang,2020).NLRs are also present in animals,including mammals。展开更多
Nucleotide-binding leucine-rich repeat (NLR) proteins serve as immune receptors in both plants and animals. To identify components required for NLR-mediated immunity, we designed and carried out a chemical genetics ...Nucleotide-binding leucine-rich repeat (NLR) proteins serve as immune receptors in both plants and animals. To identify components required for NLR-mediated immunity, we designed and carried out a chemical genetics screen to search for small molecules that can alter immune responses in Arabidopsis thaliana. From 13 600 compounds, we identified Ro 8-4304 that was able to specifically suppress the severe autoimmune phenotypes of chs3-2D (chilling sensitive 3, 2D), including the arrested growth morphology and heightened PR (Pathogenesis Related) gene expression. Further, six Ro 8-4304 insensitive mutants were uncovered from the Ro 8-4304-insensitive mutant (rim) screen using a mutagenized chs3-2D popula- tion. Positional cloning revealed thatriml encodes an allele of AtlCIn (I, currents; CI, chloride; n, nucleotide). Genetic and biochemical analysis demonstrated that AtlCIn is in the same protein complex with the meth- ylosome components small nuclear ribonucleoprotein D3b (SmD3b) and protein arginine methyltransferase 5 (PRMT5), which are required for the biogenesis of small nuclear ribonucleoproteins (snRNPs) involved in mRNA splicing. Double mutant analysis revealed that SmD3b is also involved in the sensitivity to Ro 8-4304, and the prmt5-1 chs3-2D double mutant is lethal. Loss of At/C/n, SmD3b, or PRMT5 function results in enhanced disease resistance against the virulent oomycete pathogen Hyaloperonospora arabidopsidis Noco2, suggesting that mRNA splicing plays a previously unknown negative role in plant immunity. The successful implementation of a high-throughput chemical genetic screen and the identification of a small-molecule compound affecting plant immunity indicate that chemical genetics is a powerful tool to study whole-organism plant defense pathways.展开更多
Dear Editor, Upon recognition of pathogen effectors, plant resist- ance (R) proteins trigger strong defense responses that restrict the growth and spread of pathogens. Most R pro- teins are nucleotide-binding (NB...Dear Editor, Upon recognition of pathogen effectors, plant resist- ance (R) proteins trigger strong defense responses that restrict the growth and spread of pathogens. Most R pro- teins are nucleotide-binding (NB) and leucine-rich repeat (LRR) domain-containing proteins (NLRs) sharing struc- tural similarity with animal NOD-like receptors (Dodds and Rathjen, 2010). SNC1 (Suppressor of nprl, constitutive 1) is an Arabidopsis Toll/interleukin-1 Receptor (TIR)-type NLR that was originally identified through a gain-of-function autoimmune mutant, sncl, from a forward genetic screen.展开更多
A double lipid bilayer separating the nucleus from the cytoplasm,termed the nuclear envelope,is a defining feature of eukaryotes.Nucleocytoplasmic transport of macromolecules through the nuclear pores enables fine-tun...A double lipid bilayer separating the nucleus from the cytoplasm,termed the nuclear envelope,is a defining feature of eukaryotes.Nucleocytoplasmic transport of macromolecules through the nuclear pores enables fine-tuned regulation of biologic processes.All mature mRNAs are delivered to the cytoplasm from the nucleus via an mRNA export pathway.Much work has been done in yeast and animals to study the machinery of mRNA export.However,until recently,research on plant mRNA export has been quite limited.Genetic,bioinformatic,and biochemical investigations have expanded our understanding of the mRNA export process in plants.Here,we review recent progress that has been made elucidating the components of the mRNA export pathway in plants.MOS3(MODIFIER OF SNC1,3)/AtNup96 and AtNup160 are both components of the highly conserved Nup107-160 nucleoporin complex and were shown to play key roles in mRNA export.MOS11(MODIFIER OF SNC1,11),which is homologous to the RNA helicase enhancer CIP29 in human,was recently found to be involved in the same pathway as MOS3.A DEAD Box RNA helicase,LOS4(low expression of osmotically responsive genes 4)was also found to play a role in the mRNA export process,putatively by carrying mRNA molecules through the nuclear envelope.Recently,a protein complex homologous to the yeast TREX-2 complex was also found to play important roles in mRNA export in plants.It appears that most players in the mRNA export pathway are highly conserved among plants,yeast and animals.展开更多
基金The Natural Sciences and Engineering Research Council of Canada(NSERC)-Discovery and NSERC-CREATE PRoTECT programs provide us with financial supportsupported by scholarships from MSL Graduate Student Award and China Scholarship Council.
文摘Plant intracellular nucleotide-binding domain leucine-rich repeat(NLR)receptors play crucial roles in immune responses against pathogens.How diverse NLRs recognize different pathogen effectors remains a significant ques-tion.A recent study published in Nature uncovered how pepper NLR Tsw detects phytohormone receptors’interfer-ence caused by tomato spotted wilt virus(TSWV)effector,triggering a robust immune response,showcasing a new manner of NLR guarding.
文摘N-Hydroxypipecolic acid(NHP)is a signaling molecule crucial for systemic acquired resistance(SAR),a systemic immune response in plants that provides long-lasting and broad-spectrum protection against secondary pathogen infections.To identify negative regulators of NHP biosynthesis,we performed a forward genetic screen to search for mutants with elevated expression of the NHP biosynthesis gene FLAVIN-DEPENDENT MONOOXYGENASE 1(FMO1).Analysis of two constitutive expression of FMO1(cef)and one induced expression of FMO1(ief)mutants revealed that the AIPP3–PHD2–CPL2 protein complex,which is involved in the recognition of the histone modification H3K27me3 and transcriptional repression,contributes to the negative regulation of FMO1 expression and NHP biosynthesis.Our study suggests that epigenetic regulation plays a crucial role in controlling FMO1 expression and NHP levels in plants.
基金The study was supported by the Fundamental Research Funds for the National Natural Science Foundation of China(Nos.82104376,82073998,22177084,and 82104373)the Xinglin Scholar Research Premotion Project of Chengdu University of TCM,the Open Research Fund of Chengdu University of Traditional Chinese Medicine State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China,the Fundamental Research Funds of Science&Technology Department of Sichuan Province(Nos.2022NSFSC0626,2023NSFSC1108)the Postdoctoral Research Project of Sichuan Province.
文摘Undruggable proteins are a class of proteins that are often characterized by large,complex structures or functions that are diffcult to interfere with using conventional drug design strategies.Targeting such undruggable targets has been considered also a great opportunity for treatment of human diseases and has attracted substantial efforts in the field of medicine.Therefore,in this review,we focus on the recent development of drug discovery targeting"undruggable"proteins and their application in clinic.To make this review well organized,we discuss the design strategies targeting the undruggable proteins,including covalent regulation,allosteric inhibition,protein-protein/DNA interaction inhibition,targeted proteins regulation,nucleic acid-based approach,immunotherapy and others.
基金Research on conifer defense in the laboratory of J.B. has been generously supported with Discovery and Strategic Research Grants from the Natural Sciences and Engineering Research Council of Canada, and with funding from Genome British Columbia and Genome Canada for the Treenomix Conifer Forest Health project (www.treenomix.ca) and the Tria Project (www.thetriaproject.ca)
文摘Defense-related terpenoid biosynthesis in conifers is a dynamic process closely associated with specialized anatomical structures that allows conifers to cope with attack from many potential pests and pathogens. The constitutive and inducible terpenoid defense of conifers involves several hundred different monoterpenes, sesquiterpenes and diterpenes. Changing arrays of these many compounds are formed from the general isoprenoid pathway by activities of large gene families for two classes of enzymes, the terpene synthases and the cytochrome P450-dependent monooxygenases of the CYP720B group. Extensive studies have been conducted on the genomics, proteomics and molecular biochemical characterization of these enzymes. Many of the conifer terpene synthases are multi-product enzymes, and the P450 enzymes of the CYP720B group are promiscuous in catalyzing multiple oxidations, along homologous series of diterpenoids, from a broad spectrum of substrates. The terpene synthases and CYP720B genes respond to authentic or simulated insect attack with increased transcript levels, protein abundance and enzyme activity. The constitutive and induced oleoresin terpenoids for conifer defense accumulate in preformed cortical resin ducts and in xylem trauma-associated resin ducts. Formation of these resin ducts de novo in the cambium zone and developing xylem, following insect attack or treatment of trees with methyl jasmonate, is a unique feature of the induced defense of long-lived conifer trees.
文摘Salicylic acid(SA)has long been known to be essential for basal defense and systemic acquired resistance(SAR).N-Hydroxypipecolic acid(NHP),a recently discovered plant metabolite,also plays a key role in SAR and to a lesser extent in basal resistance.Following pathogen infection,levels of both compounds are dramatically increased.Analysis of SA-or SAR-deficient mutants has uncovered how SA and NHP are biosynthesized.The completion of the SA and NHP biosynthetic pathways in Arabidopsis allowed better understanding of how they are regulated.In this review,we discuss recent progress on SA and NHP biosynthesis and their regulation in plant immunity.
文摘Two signal molecules, salicylic acid (SA) and N-hydroxypipecolic acid (NHP), play critical roles in plant immunity. The biosynthetic genes of both compounds are positively regulated by master immune-regulating transcription factors SARD1 and CBP60g. However, the relationship between the SA and NHP pathways is unclear. CALMODULIN-BINDING TRANSCRIPTION FACTOR 1 (CAMTA1), CAMTA2, and CAMTA3 are known redundant negative regulators of plant immunity, but the underlying mechanism also remains largely unknown. In this study, through chromatin immunoprecipitation and electrophoretic mobility shift assays, we uncovered that CBP60g is a direct target of CAMTA3, which also negatively regulates the expression of SARD1, presumably via an indirect effect. The autoimmunity of camta3-1 is suppressed by sard1 cbp60g double mutant as well as ald1 and fmo1, two single mutants defective in NHP biosynthesis. Interestingly, a suppressor screen conducted in the camta1/ 2/ 3 triple mutant background yielded various mutants blocking biosynthesis or signaling of either SA or NHP, leading to nearly complete suppression of the extreme autoimmunity of camta1/ 2/ 3, suggesting that the SA and NHP pathways can mutually amplify each other. Together, these results reveal that CAMTAs repress the biosynthesis of SA and NHP by modulating the expression of SARD1 and CBP60g, and that the SA and NHP pathways are coordinated to optimize plant immune response.
基金supported by grants from the Natural Sciences and Engineering Research Council of Canada(NSERC)Discovery programthe Dewar Cooper Memorial Fund from the University of British Columbia(UBC)+1 种基金partially supported by a 4YF scholarship from UBCpartially supported by a Chinese Scholarship Council(CSC)fellowship
文摘Summary Salicylic acid (SA) is an essential defence hormone in plants. Upon pathogen infection, induced biosynthesis of SA is mediated by Isochorismate synthase 1 (ICS1), whose gene transcription is controlled mainly through two redundant transcription factors, SAR Deficient 1 (SARD0 and Calmodulin- binding protein 6o-like g (CBP60g).
文摘Arabidopsis SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1(SARD1)and CALMODULIN-BINDING PROTEIN 60g(CBP60g)are two master transcription factors that regulate many defense-related genes in plant immunity.They are required for immunity downstream of the receptor-like protein SUPPRESSOR OF NPR1-1,CONSTITUTIVE 2(SNC2).Constitutive defense responses in the gain-of-function autoimmune snc2-1D mutant are modestly affected in either sard1 or cbp60g single mutants but completely suppressed in the sard1 cbp60g double mutant.Here we report that CBP60b,another member of the CBP60 family,also functions as a positive regulator of SNC2-mediated immunity.Loss-of-function mutations of CBP60b suppress the constitutive expression of SARD1 and enhanced disease resistance in cbp60g-1 snc2-1D,whereas overexpression of CBP60b leads to elevated SARD1 expression and constitutive defense responses.In addition,transient expression of CBP60b in Nicotiana benthamiana activates the expression of the pSARD1::luciferase reporter gene.Chromatin immunoprecipitation assays further showed that CBP60b is recruited to the promoter region of SARD1,suggesting that it directly regulates SARD1 expression.Interestingly,knocking out CBP60b in the wild-type background leads to ENHANCED DISEASE SUSCEPTIBILITY 1(EDS1)-dependent autoimmunity,suggesting that CBP60b is required for the expression of a guardee/decoy or a negative regulator of immunity mediated by receptors carrying an N-terminal Toll-interleukin-1 receptor-like domain.
基金This review was supported by the Key-Area Research and Development Program of Guangdong Province(2018B030331001)the National Natural Science Foundation of China(31630031 and 31930047)+3 种基金the Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence Fund(2019025),the Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)the Chinese Academy of Sciences International Partnership Program(172644KYSB20170004)the CAS President’s International Fellowship for Distinguished Scientists(2021DB0003)the Canadian Institutes of Health Research(#10677).
文摘The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across vertebrate evolution.Moreover,cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors.This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets.We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions.The systematic delineation of SC organization,cell types,and neural connections is further put into context across species as these depend upon laminar architecture.Moreover,we focus on SC neural circuitry involving saccadic eye movement,and cognitive and innate behaviors.Overall,the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.
基金the financial support to S.X.from the National Natural Science Foundation of China(31971836)the Hunan provincial Natural Science Foundation(2019JJ40126)the financial support to Y.Z.from NSERC Discovery grant program。
文摘Higher plants utilize a variety of immune receptors to recognize pathogens and trigger defense responses.Intracellular nucleotidebinding leucine-rich repeat receptors(NLRs)are widely used for detecting pathogen effectors(Jones et al.,2016;Zhou and Zhang,2020).NLRs are also present in animals,including mammals。
文摘Nucleotide-binding leucine-rich repeat (NLR) proteins serve as immune receptors in both plants and animals. To identify components required for NLR-mediated immunity, we designed and carried out a chemical genetics screen to search for small molecules that can alter immune responses in Arabidopsis thaliana. From 13 600 compounds, we identified Ro 8-4304 that was able to specifically suppress the severe autoimmune phenotypes of chs3-2D (chilling sensitive 3, 2D), including the arrested growth morphology and heightened PR (Pathogenesis Related) gene expression. Further, six Ro 8-4304 insensitive mutants were uncovered from the Ro 8-4304-insensitive mutant (rim) screen using a mutagenized chs3-2D popula- tion. Positional cloning revealed thatriml encodes an allele of AtlCIn (I, currents; CI, chloride; n, nucleotide). Genetic and biochemical analysis demonstrated that AtlCIn is in the same protein complex with the meth- ylosome components small nuclear ribonucleoprotein D3b (SmD3b) and protein arginine methyltransferase 5 (PRMT5), which are required for the biogenesis of small nuclear ribonucleoproteins (snRNPs) involved in mRNA splicing. Double mutant analysis revealed that SmD3b is also involved in the sensitivity to Ro 8-4304, and the prmt5-1 chs3-2D double mutant is lethal. Loss of At/C/n, SmD3b, or PRMT5 function results in enhanced disease resistance against the virulent oomycete pathogen Hyaloperonospora arabidopsidis Noco2, suggesting that mRNA splicing plays a previously unknown negative role in plant immunity. The successful implementation of a high-throughput chemical genetic screen and the identification of a small-molecule compound affecting plant immunity indicate that chemical genetics is a powerful tool to study whole-organism plant defense pathways.
文摘Dear Editor, Upon recognition of pathogen effectors, plant resist- ance (R) proteins trigger strong defense responses that restrict the growth and spread of pathogens. Most R pro- teins are nucleotide-binding (NB) and leucine-rich repeat (LRR) domain-containing proteins (NLRs) sharing struc- tural similarity with animal NOD-like receptors (Dodds and Rathjen, 2010). SNC1 (Suppressor of nprl, constitutive 1) is an Arabidopsis Toll/interleukin-1 Receptor (TIR)-type NLR that was originally identified through a gain-of-function autoimmune mutant, sncl, from a forward genetic screen.
文摘A double lipid bilayer separating the nucleus from the cytoplasm,termed the nuclear envelope,is a defining feature of eukaryotes.Nucleocytoplasmic transport of macromolecules through the nuclear pores enables fine-tuned regulation of biologic processes.All mature mRNAs are delivered to the cytoplasm from the nucleus via an mRNA export pathway.Much work has been done in yeast and animals to study the machinery of mRNA export.However,until recently,research on plant mRNA export has been quite limited.Genetic,bioinformatic,and biochemical investigations have expanded our understanding of the mRNA export process in plants.Here,we review recent progress that has been made elucidating the components of the mRNA export pathway in plants.MOS3(MODIFIER OF SNC1,3)/AtNup96 and AtNup160 are both components of the highly conserved Nup107-160 nucleoporin complex and were shown to play key roles in mRNA export.MOS11(MODIFIER OF SNC1,11),which is homologous to the RNA helicase enhancer CIP29 in human,was recently found to be involved in the same pathway as MOS3.A DEAD Box RNA helicase,LOS4(low expression of osmotically responsive genes 4)was also found to play a role in the mRNA export process,putatively by carrying mRNA molecules through the nuclear envelope.Recently,a protein complex homologous to the yeast TREX-2 complex was also found to play important roles in mRNA export in plants.It appears that most players in the mRNA export pathway are highly conserved among plants,yeast and animals.