Diderm bacteria,characterized by an additional lipid membrane layer known as the outer membrane,fold their outer membrane proteins(OMPs)via theβ-barrel assembly machinery(BAM)complex.Understanding how the BAM complex...Diderm bacteria,characterized by an additional lipid membrane layer known as the outer membrane,fold their outer membrane proteins(OMPs)via theβ-barrel assembly machinery(BAM)complex.Understanding how the BAM complex,particularly its key component BamA,assists in OMP folding remains crucial in bacterial cell biology.Recent research has focused primarily on the structural and functional characteristics of BamA within the Gracilicutes clade,such as in Escherichia coli(E.coli).However,another major evolutionary branch,Terrabacteria,has received comparatively less attention.An example of a Terrabacteria is Deinococcus radiodurans(D.radiodurans),a Gram-positive bacterium that possesses a distinctive outer membrane structure.In this study,we first demonstrated that theβ-barrel domains of BamA are not interchangeable between D.radiodurans and E.coli.The structure of D.radiodurans BamA was subsequently determined at 3.8Åresolution using cryo-electron microscopy,revealing obviously distinct arrangements of extracellular loop 4(ECL4)and ECL6 after structural comparison with their counterparts in gracilicutes.Despite the overall similarity in the topology of theβ-barrel domain,our results indicate that certain ECLs have evolved into distinct structures between the Terrabacteria and Gracilicutes clades.While BamA and its function are generally conserved across diderm bacterial species,our findings underscore the evolutionary diversity of this core OMP folder among bacteria,offering new insights into bacterial physiology and evolutionary biology.展开更多
1|CURRENT UNDERSTANDING OF LNCRNAS Long non-coding RNAs(lncRNAs)are a class of regulatory RNA molecules that have captured the attention of researchers in recent years due to their diverse roles in development,physiol...1|CURRENT UNDERSTANDING OF LNCRNAS Long non-coding RNAs(lncRNAs)are a class of regulatory RNA molecules that have captured the attention of researchers in recent years due to their diverse roles in development,physiological and pathological processes.展开更多
Zeste white 10(ZW10)was first identified as a centromere/kinetochore protein encoded by the ZW10 gene in Drosophila.ZW10 guides the spindle assembly checkpoint signaling during mitotic chromosome segregation in metazo...Zeste white 10(ZW10)was first identified as a centromere/kinetochore protein encoded by the ZW10 gene in Drosophila.ZW10 guides the spindle assembly checkpoint signaling during mitotic chromosome segregation in metazoans.Recent studies have shown that ZW10 is also involved in membrane-bound organelle interactions during interphase and plays a vital role in membrane transport between the endoplasmic reticulum and Golgi apparatus.Despite these findings,the precise molecular mechanisms by which ZW10 regulates interactions between membrane-bound organelles in interphase and the assembly of membraneless organelle kinetochore in mitosis remain elusive.Here,we highlight how ZW10 forms context-dependent protein complexes during the cell cycle.These complexes are essential for mediating membrane trafficking in interphase and ensuring the accurate segregation of chromosomes in mitosis.展开更多
Dear Editor,Promyelocytic leukemia(PML)is the scaffold protein that organizes PML bod-ies,which are nuclear membraneless organelles involved in various biologi-cal processes,including tumor suppres-sion and antiviral ...Dear Editor,Promyelocytic leukemia(PML)is the scaffold protein that organizes PML bod-ies,which are nuclear membraneless organelles involved in various biologi-cal processes,including tumor suppres-sion and antiviral responses(Ugge et al.,2022).Early electron microscopic analy-ses revealed contacts between the sur-face of PML bodies and chromatin struc-ture(Corpet et al.,2020).In fact,sev-eral chromatin and cell cycle regulators,such as TIP60,P300,and heterochro-matin protein 1(HP1),are localized in PML bodies in interphase cells(Corpet et al.,2020).展开更多
Although the dynamic instability of microtubules(MTs)is fundamental to many cellular functions,quiescent MTs with unattached free distal ends are commonly present and play important roles in various events to power ce...Although the dynamic instability of microtubules(MTs)is fundamental to many cellular functions,quiescent MTs with unattached free distal ends are commonly present and play important roles in various events to power cellular dynamics.However,how these free MT tips are stabilized remains poorly understood.Here,we report that centrosome and spindle pole protein 1(CSPP1)caps and stabilizes both plus and minus ends of static MTs.Real-time imaging of laser-ablated MTs in live cells showed deposition of CSPP1 at the newly generated MT ends,whose dynamic instability was concomitantly suppressed.Consistently,MT ends in CSPP1-overexpressing cells were hyper-stabilized,while those in CSPP1-depleted cells were much more dynamic.This CSPP1-elicited stabilization of MTs was demonstrated to be achieved by suppressing intrinsic MT catastrophe and restricting polymerization.Importantly,CSPP1-bound MTs were resistant to mitotic centromere-associated kinesin-mediated depolymerization.These findings delineate a previously uncharacterized CSPP1 activity that integrates MT end capping to orchestrate quiescent MTs.展开更多
Dear Editor,Biomacromolecules aggregate to form membraneless organelles(MLOs)via phase separation has been observed in a variety of physiological processes over the last decade.1 However,the molecular basis of biomacr...Dear Editor,Biomacromolecules aggregate to form membraneless organelles(MLOs)via phase separation has been observed in a variety of physiological processes over the last decade.1 However,the molecular basis of biomacromolecule phase separation in cells and assembly modes of this process remain largely unknown due to a lack of available experimental methods.The dynamics of different MLOs vary widely.展开更多
The 2-hydroxy-4-methoxybenzyl(Hmb)backbone modification can prevent amide bond-mediated sidereactions(e.g.,aspartimide formation,peptide aggregation)by installing the removable Hmb group into a peptide bond,thus impro...The 2-hydroxy-4-methoxybenzyl(Hmb)backbone modification can prevent amide bond-mediated sidereactions(e.g.,aspartimide formation,peptide aggregation)by installing the removable Hmb group into a peptide bond,thus improving the synthesis of long and challenging peptides and proteins.However,its use is largely precluded by the limited Hmb’s installation sites.In this report,an improved installation of Hmb(iHmb)method was developed to achieve the flexible installation and the convenient removal of Hmb.The iHmb method involves two critical steps:(1)oxidative diazotization of the readily installed 2-hydroxy-4-methoxy-5-amino-benzyl(Hmab)to give 2-hydroxy-4-methoxy-5-diazonium-benzyl(Hmdab)by combining soamyl nitrite(IAN)/HBF_(4),and(2)reductive elimination of Hmdab to give the desired Hmb by 1,2-ethanedithiol(EDT).The iHmb method enables the installation of Hmb at any primary amino acid including the highly sterically hindered amino acids(e.g.,valine and isoleucine).The practicality and utility of the iHmb method was demonstrated by one-shot solid-phase synthesis of a challenging aspartimide-prone peptide,the mirror-image version of a hydrophobic peptide and a long-chain peptide up to 76-residue.Furthermore,the iHmb method can be utilized to facilitate chemical protein ligation,as exemplified by the synthesis of the single-spanning membrane protein sarcolipin.The iHmb method expands the toolkit for peptide synthesis and ligation and facilitates the preparation of peptides/proteins.展开更多
The oxidative pentose phosphate(OPP)pathway provides metabolic intermediates for the shikimate pathway and directs carbon flow to the biosynthesis of aromatic amino acids(AAAs),which serve as basic protein building bl...The oxidative pentose phosphate(OPP)pathway provides metabolic intermediates for the shikimate pathway and directs carbon flow to the biosynthesis of aromatic amino acids(AAAs),which serve as basic protein building blocks and precursors of numerous metabolites essential for plant growth.However,genetic evidence linking the two pathways is largely unclear.In this study,we identified 6-phosphogluconate dehydrogenase 2(PGD2),the rate-limiting enzyme of the cytosolic OPP pathway,through suppressor screening of arogenate dehydrogenase 2(adh2)in Arabidopsis.Our data indicated that a single amino acid substitution at position 63(glutamic acid to lysine)of PGD2 enhanced its enzyme activity by facilitating the dissociation of products from the active site of PGD2,thus increasing the accumulation of AAAs and partially restoring the defective phenotype of adh2.Phylogenetic analysis indicated that the point mutation occurred in a well-conserved amino acid residue.Plants with different amino acids at this conserved site of PGDs confer diverse catalytic activities,thus exhibiting distinct AAAs producing capability.These findings uncover the genetic link between the OPP pathway and AAAs biosynthesis through PGD2.The gain-of-function point mutation of PGD2 identified here could be considered as a potential engineering target to alter the metabolic flux for the production of AAAs and downstream compounds.展开更多
Crop yield plays a critical role in global food security.For optimal plant growth and maximal crop yields,nutrients must be balanced.However,the potential significance of balanced nitrogen-iron(N-Fe)for improving crop...Crop yield plays a critical role in global food security.For optimal plant growth and maximal crop yields,nutrients must be balanced.However,the potential significance of balanced nitrogen-iron(N-Fe)for improving crop yield and nitrogen use efficiency(NUE)has not previously been addressed.Here,we show that balanced N-Fe sufficiency significantly increases tiller number and boosts yield and NUE in rice and wheat.NIN-like protein 4(OsNLP4)plays a pivotal role in maintaining the N-Fe balance by coordinately regulating the expression of multiple genes involved in N and Fe metabolism and signaling.OsNLP4 also suppresses OsD3 expression and strigolactone(SL)signaling,thereby promoting tillering.Balanced N-Fe sufficiency promotes the nuclear localization of OsNLP4 by reducing H_(2)O_(2) levels,reinforcing the functions of OsNLP4.Interestingly,we found that OsNLP4 upregulates the expression of a set of H2O2-scavenging genes to promote its own accumulation in the nucleus.Furthermore,we demonstrated that foliar spraying of balanced N-Fe fertilizer at the tillering stage can effectively increase tiller number,yield,and NUE of both rice and wheat in the field.Collectively,these findings reveal the previously unrecognized effects of N-Fe balance on grain yield and NUE as well as the molecular mechanism by which the OsNLP4-OsD3 module integrates N-Fe nutrient signals to downregulate SL signaling and thereby promote rice tillering.Our study sheds light on how N-Fe nutrient signals modulate rice tillering and provide potential innovative approaches that improve crop yield with reduced N fertilizer input for benefitting sustainable agriculture worldwide.展开更多
Paraquat(PQ)is the third most used broad-spectrum nonselective herbicide around the globe after glyphosate and glufosinate.Repeated usage and overreliance on this herbicide have resulted in the emergence of PQ-resista...Paraquat(PQ)is the third most used broad-spectrum nonselective herbicide around the globe after glyphosate and glufosinate.Repeated usage and overreliance on this herbicide have resulted in the emergence of PQ-resistant weeds that are a potential hazard to agriculture.It is generally believed that PQ resistance in weeds is due to increased sequestration of the herbicide and its decreased translocation to the target site,as well as an enhanced ability to scavenge reactive oxygen species.However,little is known about the genetic bases and molecular mechanisms of PQ resistance in weeds,and hence no PQ-resistant crops have been developed to date.Forward genetics of the model plant Arabidopsis thaliana has advanced our understanding of the molecular mechanisms of PQ resistance.This review focuses on PQ resistance loci and resistance mechanisms revealed in Arabidopsis and examines the possibility of developing PQ-resistant crops using the elucidated mechanisms.展开更多
Protein kinases regulate virtually all cellular processes,but it remains challenging to determine the functions of all protein kinases,collectively called the“kinome”,in any species.We developed a computational appr...Protein kinases regulate virtually all cellular processes,but it remains challenging to determine the functions of all protein kinases,collectively called the“kinome”,in any species.We developed a computational approach called EXPLICIT-Kinase to predict the functions of the Arabidopsis kinome.Because the activities of many kinases can be regulated transcriptionally,their gene expression patterns provide clues to their functions.A universal gene expression predictor for Arabidopsis was constructed to predict the expression of 30,172 nonkinase genes based on the expression of 994 kinases.The model reconstituted highly accurate transcriptomes for diverse Arabidopsis samples.It identified the significant kinases as predictor kinases for predicting the expression of Arabidopsis genes and pathways.Strikingly,these predictor kinases were often regulators of related pathways,as exemplified by those involved in cytokinesis,tissue development,and stress responses.Comparative analyses revealed that portions of these predictor kinases are shared and conserved between Arabidopsis and maize.As an example,we identified a conserved predictor kinase,RAF6,from a stomatal movement module.We verified that RAF6 regulates stomatal closure.It can directly interact with SLAC1,a key anion channel for stomatal closure,and modulate its channel activity.Our approach enables a systematic dissection of the functions of the Arabidopsis kinome.展开更多
Dear Editor,Hand,foot,and mouth disease(HFMD)is a common illness among children that is usually mild and self-limiting.However,in some severe cases,patients may rapidly develop neurological and systemic complications ...Dear Editor,Hand,foot,and mouth disease(HFMD)is a common illness among children that is usually mild and self-limiting.However,in some severe cases,patients may rapidly develop neurological and systemic complications that can be fatal(Ooi et al.,2010).HFMD is caused by a few serotypes of human enterovirus A(HEV-A)species(Yu and Cowling,2019),with enterovirus A71(EV-A71)and coxsackievirus A16(CV-A16)being the most typical causative agents(Yu and Cowling,2019).Furthermore,severe neurological sequelae are more common in cases with EV-A71 serotype infection than other serotypes(Ooi et al.,2010;Yu and Cowling,2019).There has been a significant increase in EV-A71 epidemic activity throughout the Asia–Pacific region(McMinn,2002)since EV-A71 was first isolated from a patient with central nervous system(CNS)disease in 1969(Schmidt et al.,1974).EV-A71 is a small non-enveloped virus belonging to HEV-A species of the genus Enterovirus in the family Picornaviridae(Nasri et al.,2007).Its genome is a single-stranded positive-sense RNA of approximately 7400 bp in length and contains only one complete open reading frame(ORF),which encodes a large polyprotein(Solomon et al.,2010).展开更多
Stable transmission of genetic information during cell division requires faithful chromosome segregation.Mounting evidence has demonstrated that polo-like kinase 1(PLK1)dynamics at kinetochores control correct kinetoc...Stable transmission of genetic information during cell division requires faithful chromosome segregation.Mounting evidence has demonstrated that polo-like kinase 1(PLK1)dynamics at kinetochores control correct kinetochore–microtubule attachments and subsequent silencing of the spindle assembly checkpoint.However,the mechanisms underlying PLK1-mediated silencing of the spindle checkpoint remain elusive.Here,we identified a regulatory mechanism by which PLK1-elicited zeste white 10(ZW10)phosphorylation regulates spindle checkpoint silencing in mitosis.ZW10 is a cognate substrate of PLK1,and the phosphorylation of ZW10 at Ser12 enables dynamic ZW10–Zwint1 interactions.Inhibition of ZW10 phosphorylation resulted in misaligned chromosomes,while persistent expression of phospho-mimicking ZW10 mutant caused premature anaphase,in which sister chromatids entangled as cells entered anaphase.These findings reveal the previously uncharacterized PLK1–ZW10 interaction through which dynamic phosphorylation of ZW10 fine-tunes accurate chromosome segregation in mitosis.展开更多
Shen Chromothripsis,a type of complex chromosomal rearrangement originally known as chromoanagenesis,has been a subject of extensive investigation due to its potential role in various diseases,particularly cancer.Chro...Shen Chromothripsis,a type of complex chromosomal rearrangement originally known as chromoanagenesis,has been a subject of extensive investigation due to its potential role in various diseases,particularly cancer.Chromothripsis involves the rapid acquisition of tens to hundreds of structural rearrangements within a short period,leading to complex alterations in one or a few chromosomes.This phenomenon is triggered by chromosome mis-segregation during mitosis.Errors in accurate chromosome segregation lead to formation of aberrant structural entities such as micronuclei or chromatin bridges.The association between chromothripsis and cancer has attracted significant interest,with potential implications for tumorigenesis and disease prognosis.This review aims to explore the intricate mechanisms and consequences of chromothripsis,with a specific focus on its association with mitotic perturbations.Herein,we discuss a comprehensive analysis of crucial molecular entities and pathways,exploring the intricate roles of the CIP2A–TOPBP1 complex,micronuclei formation,chromatin bridge processing,DNA damage repair,and mitotic checkpoints.Moreover,the review will highlight recent advancements in identifying potential therapeutic targets and the underlying molecular mechanisms associated with chromothripsis,paving the way for future therapeutic interventions in various diseases.展开更多
Throughout the history of agriculture,the challenge of weed management has endured,necessitating significant investments to facilitate ideal crop growth and maximize yields.Strategies for weed control mainly involve m...Throughout the history of agriculture,the challenge of weed management has endured,necessitating significant investments to facilitate ideal crop growth and maximize yields.Strategies for weed control mainly involve manual and chemical methodologies.While manual weeding persists in certain regions,chemical herbicides notably represent the primary approach.展开更多
Paraquat is one of the most widely used nonselective herbicides and has elicited the emergence of para-quat-resistant weeds.However,the molecular mechanisms of paraquat resistance are not completely un-derstood.Here w...Paraquat is one of the most widely used nonselective herbicides and has elicited the emergence of para-quat-resistant weeds.However,the molecular mechanisms of paraquat resistance are not completely un-derstood.Here we report the Arabidopsis gain-of-function mutant pqt15-D with significantly enhanced resistance to paraquat and the corresponding gene PQT15,which encodes the Multidrug and Toxic Extru-sion(MATE)transporter DTX6.A point mutation at+932 bp in DTX6 causes a G311E amino acid substitution,enhancing the paraquat resistance ofpqt15-D,and overexpression of DTX6/PQT15 in the wild-type plants also results in strong paraquat resistance.Moreover,heterologous expression of DTX6 and DTX6-D in Es-cherichia coil significantly enhances bacterial resistance to paraquat.Importantly,overexpression of DTX6-D enables Arabidopsis plants to tolerate 4 mM paraquat,a near-commercial application level.DTX6/PQT15 is localized in the plasma membrane and endomembrane,and functions as a paraquat efflux transporter as demonstrated by paraquat efflux assays with isolated protoplasts and bacterial cells.Taken together,our results demonstrate that DTX6/PQT15 is an efflux transporter that confers paraquat resis-tance by exporting paraquat out of the cytosol.These findings reveal a molecular mechanism of paraquat resistance in higher plants and provide a promising candidate gene for engineering paraquat-resistant crops.展开更多
Salt stress is a major constraint on plant growth and yield.Nitrogen(N)fertilizers are known to alleviate salt stress.However,the underlying molecular mechanisms remain unclear.Here,we show that nitratedependent salt ...Salt stress is a major constraint on plant growth and yield.Nitrogen(N)fertilizers are known to alleviate salt stress.However,the underlying molecular mechanisms remain unclear.Here,we show that nitratedependent salt tolerance is mediated by OsMADS27 in rice.The expression of OsMADS27 is specifically induced by nitrate.The salt-inducible expression of OsMADS27 is also nitrate dependent.OsMADS27 knockout mutants are more sensitive to salt stress than the wild type,whereas OsMADS27 overexpression lines are more tolerant.Transcriptomic analyses revealed that OsMADS27 upregulates the expression of a number of known stress-responsive genes as well as those involved in ion homeostasis and antioxidation.We demonstrate that OsMADS27 directly binds to the promoters of OsHKT1.1 and OsSPL7 to regulate their expression.Notably,OsMADS27-mediated salt tolerance is nitrate dependent and positively correlated with nitrate concentration.Our results reveal the role of nitrate-responsive OsMADS27 and its downstream target genes in salt tolerance,providing a molecular mechanism for the enhancement of salt tolerance by nitrogen fertilizers in rice.OsMADS27 overexpression increased grain yield under salt stress in the presence of sufficient nitrate,suggestingthatOsMADS27 is a promising candidate for the improvementof salt tolerance inrice.展开更多
Paraquat(1,1’-dimethyl-4,4’-bipyridinium dichloride,PQ)has been widely used as a broad spectrum nonselective herbicide in agriculture for decades(Baldwin et al.,1968).Plants absorb PQ from their environment and tran...Paraquat(1,1’-dimethyl-4,4’-bipyridinium dichloride,PQ)has been widely used as a broad spectrum nonselective herbicide in agriculture for decades(Baldwin et al.,1968).Plants absorb PQ from their environment and transport to the chloroplasts,the site of its action where it competes for electrons from photosystem I(PSI)and cyclically generates superoxide that is converted to H2O2by superoxide dismutases(SODs),resultantly accumulating a large amount of reactive oxygen species(ROS)and thereby killing plants(Farrington et al.,1973).展开更多
基金supported by the Fundamental Research Funds for the Central Universities(WK9100000063)the Fundamental Research Funds for the Central Universities(WK9100000031)+3 种基金the National Natural Science Foundation of China(32270035,32271241)the Anhui Provincial Natural Science Foundation(2208085MC40,2008085QC98)the Talent Fund Project of Biomedical Sciences and Health Laboratory of Anhui Province,University of Science and Technology of China(BJ9100000003)the start-up funding from the University of Science and Technology of China(KY9100000034,KJ2070000082).
文摘Diderm bacteria,characterized by an additional lipid membrane layer known as the outer membrane,fold their outer membrane proteins(OMPs)via theβ-barrel assembly machinery(BAM)complex.Understanding how the BAM complex,particularly its key component BamA,assists in OMP folding remains crucial in bacterial cell biology.Recent research has focused primarily on the structural and functional characteristics of BamA within the Gracilicutes clade,such as in Escherichia coli(E.coli).However,another major evolutionary branch,Terrabacteria,has received comparatively less attention.An example of a Terrabacteria is Deinococcus radiodurans(D.radiodurans),a Gram-positive bacterium that possesses a distinctive outer membrane structure.In this study,we first demonstrated that theβ-barrel domains of BamA are not interchangeable between D.radiodurans and E.coli.The structure of D.radiodurans BamA was subsequently determined at 3.8Åresolution using cryo-electron microscopy,revealing obviously distinct arrangements of extracellular loop 4(ECL4)and ECL6 after structural comparison with their counterparts in gracilicutes.Despite the overall similarity in the topology of theβ-barrel domain,our results indicate that certain ECLs have evolved into distinct structures between the Terrabacteria and Gracilicutes clades.While BamA and its function are generally conserved across diderm bacterial species,our findings underscore the evolutionary diversity of this core OMP folder among bacteria,offering new insights into bacterial physiology and evolutionary biology.
基金National Natural Science Foundation of ChinaGrant/Award Number:31970598 and 32170557+3 种基金Anhui Provincial Key Research and Development ProjectGrant/Award Number:2022e07020020Research Funds of Centre for Leading Medicine and Advanced Technologies of IHMGrant/Award Number:2023IHM01030。
文摘1|CURRENT UNDERSTANDING OF LNCRNAS Long non-coding RNAs(lncRNAs)are a class of regulatory RNA molecules that have captured the attention of researchers in recent years due to their diverse roles in development,physiological and pathological processes.
基金supported by grants from the Ministry of Science and Technology of China and the National Natural Science Foundation of China(2022YFA1303100,32090040,92254302,2022YFA0806800,W2411017,32450537,91953000,92153302,32170733,and 22177106)Plans for Major Provincial Science&Technology Projects of Anhui Province(202303a0702003)+2 种基金the Ministry of Education(IRT_17R102)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19040000)the Fundamental Research Funds for the Central Universities(KB9100000007,KB9100000006,and KB9100000013).
文摘Zeste white 10(ZW10)was first identified as a centromere/kinetochore protein encoded by the ZW10 gene in Drosophila.ZW10 guides the spindle assembly checkpoint signaling during mitotic chromosome segregation in metazoans.Recent studies have shown that ZW10 is also involved in membrane-bound organelle interactions during interphase and plays a vital role in membrane transport between the endoplasmic reticulum and Golgi apparatus.Despite these findings,the precise molecular mechanisms by which ZW10 regulates interactions between membrane-bound organelles in interphase and the assembly of membraneless organelle kinetochore in mitosis remain elusive.Here,we highlight how ZW10 forms context-dependent protein complexes during the cell cycle.These complexes are essential for mediating membrane trafficking in interphase and ensuring the accurate segregation of chromosomes in mitosis.
基金supported by grants from the Ministry of Science and Technology of the People’s Republic of China and the National Natural Science Foundation of China(2022YFA1303100,32090040,92254302,92153302,2022YFA0806800,2022YFA1302700,2017YFA0503600,31621002,91853115,21922706,22177106)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19040000)+1 种基金the Ministry of Education(IRT_17R102 and 2011340213001)the Fundamental Research Funds for the Central Universities(WK2070000194).
文摘Dear Editor,Promyelocytic leukemia(PML)is the scaffold protein that organizes PML bod-ies,which are nuclear membraneless organelles involved in various biologi-cal processes,including tumor suppres-sion and antiviral responses(Ugge et al.,2022).Early electron microscopic analy-ses revealed contacts between the sur-face of PML bodies and chromatin struc-ture(Corpet et al.,2020).In fact,sev-eral chromatin and cell cycle regulators,such as TIP60,P300,and heterochro-matin protein 1(HP1),are localized in PML bodies in interphase cells(Corpet et al.,2020).
基金supported by grants from the Ministry of Science and Technology of China and the National Natural Science Foundation of China(2022YFA1303100,32090040,92254302,2022YFA0806800,91854203,31621002,2017YFA0503600,21922706,and 92153302 to Xing Liu,2022YFA1302700 to Z.W.,32100612 to Xu Liu)the Ministry of Education of China(IRT_17R102,20113402130010,and YD2070006001 to Xing Liu)+3 种基金the Plans for Major Provincial Science&Technology Projects of Anhui Province(202303a0702003 to Xing Liu)the Fundamental Research Funds for the Central Universities(KB9100000007 and KB9100000013 to Xing Liu)University of Science and Technology of China Start-up Fund(KY9990000167 to Z.W.)Zhejiang Provincial Natural Science Foundation(LY23C070002 to W.W.)。
文摘Although the dynamic instability of microtubules(MTs)is fundamental to many cellular functions,quiescent MTs with unattached free distal ends are commonly present and play important roles in various events to power cellular dynamics.However,how these free MT tips are stabilized remains poorly understood.Here,we report that centrosome and spindle pole protein 1(CSPP1)caps and stabilizes both plus and minus ends of static MTs.Real-time imaging of laser-ablated MTs in live cells showed deposition of CSPP1 at the newly generated MT ends,whose dynamic instability was concomitantly suppressed.Consistently,MT ends in CSPP1-overexpressing cells were hyper-stabilized,while those in CSPP1-depleted cells were much more dynamic.This CSPP1-elicited stabilization of MTs was demonstrated to be achieved by suppressing intrinsic MT catastrophe and restricting polymerization.Importantly,CSPP1-bound MTs were resistant to mitotic centromere-associated kinesin-mediated depolymerization.These findings delineate a previously uncharacterized CSPP1 activity that integrates MT end capping to orchestrate quiescent MTs.
基金This work was jointly supported by grants from the National Natural Science Foundation of China(32090041,D.L.)the Major Research Plan of the National Natural Science Foundation of China(2016YFA0101200,D.L.).This work was also supported in part by the CAS Key Laboratory of Innate Immunity and Chronic Disease.We are grateful to Prof.Yucai Wang and Prof.Chunlei Cang for providing experimental instruments and equipments,especially confocal microscopes.We appreciate Prof.Wei Xiong and Dr.Yushu Ge for their help and advice in the process of writing this letter.We thank Mr.Zhao Yue for his help in the data processing process.We also thank our colleagues Ms.Yun Wang,Ms.Mengtong Qin and Ms.Yu Chen for their help during the experiment.
文摘Dear Editor,Biomacromolecules aggregate to form membraneless organelles(MLOs)via phase separation has been observed in a variety of physiological processes over the last decade.1 However,the molecular basis of biomacromolecule phase separation in cells and assembly modes of this process remain largely unknown due to a lack of available experimental methods.The dynamics of different MLOs vary widely.
基金supported by the National Key Research and Development Program of China(No.2019YFA0706900)the National Natural Science Foundation of China(Nos.22022703 and 22177108)the Collaborative Innovation Program of Hefei Science Center,CAS(No.2022HSC-CIP013).
文摘The 2-hydroxy-4-methoxybenzyl(Hmb)backbone modification can prevent amide bond-mediated sidereactions(e.g.,aspartimide formation,peptide aggregation)by installing the removable Hmb group into a peptide bond,thus improving the synthesis of long and challenging peptides and proteins.However,its use is largely precluded by the limited Hmb’s installation sites.In this report,an improved installation of Hmb(iHmb)method was developed to achieve the flexible installation and the convenient removal of Hmb.The iHmb method involves two critical steps:(1)oxidative diazotization of the readily installed 2-hydroxy-4-methoxy-5-amino-benzyl(Hmab)to give 2-hydroxy-4-methoxy-5-diazonium-benzyl(Hmdab)by combining soamyl nitrite(IAN)/HBF_(4),and(2)reductive elimination of Hmdab to give the desired Hmb by 1,2-ethanedithiol(EDT).The iHmb method enables the installation of Hmb at any primary amino acid including the highly sterically hindered amino acids(e.g.,valine and isoleucine).The practicality and utility of the iHmb method was demonstrated by one-shot solid-phase synthesis of a challenging aspartimide-prone peptide,the mirror-image version of a hydrophobic peptide and a long-chain peptide up to 76-residue.Furthermore,the iHmb method can be utilized to facilitate chemical protein ligation,as exemplified by the synthesis of the single-spanning membrane protein sarcolipin.The iHmb method expands the toolkit for peptide synthesis and ligation and facilitates the preparation of peptides/proteins.
基金supported by the National Key Research and Development Program of China(2019YFA0903900)the National Natural Science Foundation of China(32300233)+1 种基金Guangdong Provincial Key Laboratory of Synthetic Genomics(2023B1212060054)Shenzhen Key Laboratory of Synthetic Genomics(ZDSYS201802061806209).
文摘The oxidative pentose phosphate(OPP)pathway provides metabolic intermediates for the shikimate pathway and directs carbon flow to the biosynthesis of aromatic amino acids(AAAs),which serve as basic protein building blocks and precursors of numerous metabolites essential for plant growth.However,genetic evidence linking the two pathways is largely unclear.In this study,we identified 6-phosphogluconate dehydrogenase 2(PGD2),the rate-limiting enzyme of the cytosolic OPP pathway,through suppressor screening of arogenate dehydrogenase 2(adh2)in Arabidopsis.Our data indicated that a single amino acid substitution at position 63(glutamic acid to lysine)of PGD2 enhanced its enzyme activity by facilitating the dissociation of products from the active site of PGD2,thus increasing the accumulation of AAAs and partially restoring the defective phenotype of adh2.Phylogenetic analysis indicated that the point mutation occurred in a well-conserved amino acid residue.Plants with different amino acids at this conserved site of PGDs confer diverse catalytic activities,thus exhibiting distinct AAAs producing capability.These findings uncover the genetic link between the OPP pathway and AAAs biosynthesis through PGD2.The gain-of-function point mutation of PGD2 identified here could be considered as a potential engineering target to alter the metabolic flux for the production of AAAs and downstream compounds.
基金supported by grants from the National Natural Science Foundation of China(grant no.32321001 to C.B.X.and 32100208 to J.W.)the Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDA24010303)+1 种基金the Anhui Provincial Natural Science Foundation(grant no.2108085QC103)the Fundamental Research Funds for the Central Universities(grant no.WK9100000023).
文摘Crop yield plays a critical role in global food security.For optimal plant growth and maximal crop yields,nutrients must be balanced.However,the potential significance of balanced nitrogen-iron(N-Fe)for improving crop yield and nitrogen use efficiency(NUE)has not previously been addressed.Here,we show that balanced N-Fe sufficiency significantly increases tiller number and boosts yield and NUE in rice and wheat.NIN-like protein 4(OsNLP4)plays a pivotal role in maintaining the N-Fe balance by coordinately regulating the expression of multiple genes involved in N and Fe metabolism and signaling.OsNLP4 also suppresses OsD3 expression and strigolactone(SL)signaling,thereby promoting tillering.Balanced N-Fe sufficiency promotes the nuclear localization of OsNLP4 by reducing H_(2)O_(2) levels,reinforcing the functions of OsNLP4.Interestingly,we found that OsNLP4 upregulates the expression of a set of H2O2-scavenging genes to promote its own accumulation in the nucleus.Furthermore,we demonstrated that foliar spraying of balanced N-Fe fertilizer at the tillering stage can effectively increase tiller number,yield,and NUE of both rice and wheat in the field.Collectively,these findings reveal the previously unrecognized effects of N-Fe balance on grain yield and NUE as well as the molecular mechanism by which the OsNLP4-OsD3 module integrates N-Fe nutrient signals to downregulate SL signaling and thereby promote rice tillering.Our study sheds light on how N-Fe nutrient signals modulate rice tillering and provide potential innovative approaches that improve crop yield with reduced N fertilizer input for benefitting sustainable agriculture worldwide.
基金This work was supported by grants from the National Natural Science Foundation of China(grant nos.31770273,31270302,and 30770189)。
文摘Paraquat(PQ)is the third most used broad-spectrum nonselective herbicide around the globe after glyphosate and glufosinate.Repeated usage and overreliance on this herbicide have resulted in the emergence of PQ-resistant weeds that are a potential hazard to agriculture.It is generally believed that PQ resistance in weeds is due to increased sequestration of the herbicide and its decreased translocation to the target site,as well as an enhanced ability to scavenge reactive oxygen species.However,little is known about the genetic bases and molecular mechanisms of PQ resistance in weeds,and hence no PQ-resistant crops have been developed to date.Forward genetics of the model plant Arabidopsis thaliana has advanced our understanding of the molecular mechanisms of PQ resistance.This review focuses on PQ resistance loci and resistance mechanisms revealed in Arabidopsis and examines the possibility of developing PQ-resistant crops using the elucidated mechanisms.
基金supported by grants from the National Natural Science Foundation of China(31770268)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA24010303)+1 种基金the Fundamental Research Funds for the Central Universities(WK2070000091)University of Science and Technology of China(Start-up fund to S.M.)。
文摘Protein kinases regulate virtually all cellular processes,but it remains challenging to determine the functions of all protein kinases,collectively called the“kinome”,in any species.We developed a computational approach called EXPLICIT-Kinase to predict the functions of the Arabidopsis kinome.Because the activities of many kinases can be regulated transcriptionally,their gene expression patterns provide clues to their functions.A universal gene expression predictor for Arabidopsis was constructed to predict the expression of 30,172 nonkinase genes based on the expression of 994 kinases.The model reconstituted highly accurate transcriptomes for diverse Arabidopsis samples.It identified the significant kinases as predictor kinases for predicting the expression of Arabidopsis genes and pathways.Strikingly,these predictor kinases were often regulators of related pathways,as exemplified by those involved in cytokinesis,tissue development,and stress responses.Comparative analyses revealed that portions of these predictor kinases are shared and conserved between Arabidopsis and maize.As an example,we identified a conserved predictor kinase,RAF6,from a stomatal movement module.We verified that RAF6 regulates stomatal closure.It can directly interact with SLAC1,a key anion channel for stomatal closure,and modulate its channel activity.Our approach enables a systematic dissection of the functions of the Arabidopsis kinome.
文摘Dear Editor,Hand,foot,and mouth disease(HFMD)is a common illness among children that is usually mild and self-limiting.However,in some severe cases,patients may rapidly develop neurological and systemic complications that can be fatal(Ooi et al.,2010).HFMD is caused by a few serotypes of human enterovirus A(HEV-A)species(Yu and Cowling,2019),with enterovirus A71(EV-A71)and coxsackievirus A16(CV-A16)being the most typical causative agents(Yu and Cowling,2019).Furthermore,severe neurological sequelae are more common in cases with EV-A71 serotype infection than other serotypes(Ooi et al.,2010;Yu and Cowling,2019).There has been a significant increase in EV-A71 epidemic activity throughout the Asia–Pacific region(McMinn,2002)since EV-A71 was first isolated from a patient with central nervous system(CNS)disease in 1969(Schmidt et al.,1974).EV-A71 is a small non-enveloped virus belonging to HEV-A species of the genus Enterovirus in the family Picornaviridae(Nasri et al.,2007).Its genome is a single-stranded positive-sense RNA of approximately 7400 bp in length and contains only one complete open reading frame(ORF),which encodes a large polyprotein(Solomon et al.,2010).
基金supported by grants from the Ministry of Science and Technology of China and the National Natural Science Foundation of China(2022YFA1303100,32090040,92254302,2022YFA0806800,91854203,31621002,2017YFA0503600,21922706,and 92153302 to X.L.92053104 to X.G.)+2 种基金the Plans for Major Provincial Science&Technology Projects of Anhui Province(202303a0702003 to X.L.)the Ministry of Education(IRT_17R102 to X.L.)the Fundamental Research Funds for the Central Universities(KB9100000007 and KB9100000013 to X.L.)。
文摘Stable transmission of genetic information during cell division requires faithful chromosome segregation.Mounting evidence has demonstrated that polo-like kinase 1(PLK1)dynamics at kinetochores control correct kinetochore–microtubule attachments and subsequent silencing of the spindle assembly checkpoint.However,the mechanisms underlying PLK1-mediated silencing of the spindle checkpoint remain elusive.Here,we identified a regulatory mechanism by which PLK1-elicited zeste white 10(ZW10)phosphorylation regulates spindle checkpoint silencing in mitosis.ZW10 is a cognate substrate of PLK1,and the phosphorylation of ZW10 at Ser12 enables dynamic ZW10–Zwint1 interactions.Inhibition of ZW10 phosphorylation resulted in misaligned chromosomes,while persistent expression of phospho-mimicking ZW10 mutant caused premature anaphase,in which sister chromatids entangled as cells entered anaphase.These findings reveal the previously uncharacterized PLK1–ZW10 interaction through which dynamic phosphorylation of ZW10 fine-tunes accurate chromosome segregation in mitosis.
基金supported by the Ministry of Science and Technology of China and the National Natural Science Foundation of China(2022YFA1303100,32090040,92254302,2022YFA0806800,91854203,31621002,2017YFA0503600,21922706,92153302 to X.L.,2022YFA1302700 to Z.W.)the Ministry of Education(IRT_17R102,20113402130010,YD2070006001 to X.L.)+1 种基金the Fundamental Research Funds for the Central Universities(WK2070000194 to X.L.)the University of Science and Technology of China Start-up Fund(KY9990000167 to Z.W.).
文摘Shen Chromothripsis,a type of complex chromosomal rearrangement originally known as chromoanagenesis,has been a subject of extensive investigation due to its potential role in various diseases,particularly cancer.Chromothripsis involves the rapid acquisition of tens to hundreds of structural rearrangements within a short period,leading to complex alterations in one or a few chromosomes.This phenomenon is triggered by chromosome mis-segregation during mitosis.Errors in accurate chromosome segregation lead to formation of aberrant structural entities such as micronuclei or chromatin bridges.The association between chromothripsis and cancer has attracted significant interest,with potential implications for tumorigenesis and disease prognosis.This review aims to explore the intricate mechanisms and consequences of chromothripsis,with a specific focus on its association with mitotic perturbations.Herein,we discuss a comprehensive analysis of crucial molecular entities and pathways,exploring the intricate roles of the CIP2A–TOPBP1 complex,micronuclei formation,chromatin bridge processing,DNA damage repair,and mitotic checkpoints.Moreover,the review will highlight recent advancements in identifying potential therapeutic targets and the underlying molecular mechanisms associated with chromothripsis,paving the way for future therapeutic interventions in various diseases.
文摘Throughout the history of agriculture,the challenge of weed management has endured,necessitating significant investments to facilitate ideal crop growth and maximize yields.Strategies for weed control mainly involve manual and chemical methodologies.While manual weeding persists in certain regions,chemical herbicides notably represent the primary approach.
基金supported by grants from the National Natural Science Foundation of China(grant no.31770273).
文摘Paraquat is one of the most widely used nonselective herbicides and has elicited the emergence of para-quat-resistant weeds.However,the molecular mechanisms of paraquat resistance are not completely un-derstood.Here we report the Arabidopsis gain-of-function mutant pqt15-D with significantly enhanced resistance to paraquat and the corresponding gene PQT15,which encodes the Multidrug and Toxic Extru-sion(MATE)transporter DTX6.A point mutation at+932 bp in DTX6 causes a G311E amino acid substitution,enhancing the paraquat resistance ofpqt15-D,and overexpression of DTX6/PQT15 in the wild-type plants also results in strong paraquat resistance.Moreover,heterologous expression of DTX6 and DTX6-D in Es-cherichia coil significantly enhances bacterial resistance to paraquat.Importantly,overexpression of DTX6-D enables Arabidopsis plants to tolerate 4 mM paraquat,a near-commercial application level.DTX6/PQT15 is localized in the plasma membrane and endomembrane,and functions as a paraquat efflux transporter as demonstrated by paraquat efflux assays with isolated protoplasts and bacterial cells.Taken together,our results demonstrate that DTX6/PQT15 is an efflux transporter that confers paraquat resis-tance by exporting paraquat out of the cytosol.These findings reveal a molecular mechanism of paraquat resistance in higher plants and provide a promising candidate gene for engineering paraquat-resistant crops.
基金The Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDA24010303 to C.B.X.).
文摘Salt stress is a major constraint on plant growth and yield.Nitrogen(N)fertilizers are known to alleviate salt stress.However,the underlying molecular mechanisms remain unclear.Here,we show that nitratedependent salt tolerance is mediated by OsMADS27 in rice.The expression of OsMADS27 is specifically induced by nitrate.The salt-inducible expression of OsMADS27 is also nitrate dependent.OsMADS27 knockout mutants are more sensitive to salt stress than the wild type,whereas OsMADS27 overexpression lines are more tolerant.Transcriptomic analyses revealed that OsMADS27 upregulates the expression of a number of known stress-responsive genes as well as those involved in ion homeostasis and antioxidation.We demonstrate that OsMADS27 directly binds to the promoters of OsHKT1.1 and OsSPL7 to regulate their expression.Notably,OsMADS27-mediated salt tolerance is nitrate dependent and positively correlated with nitrate concentration.Our results reveal the role of nitrate-responsive OsMADS27 and its downstream target genes in salt tolerance,providing a molecular mechanism for the enhancement of salt tolerance by nitrogen fertilizers in rice.OsMADS27 overexpression increased grain yield under salt stress in the presence of sufficient nitrate,suggestingthatOsMADS27 is a promising candidate for the improvementof salt tolerance inrice.
基金supported by the National Natural Science Foundation of China(31770273)。
文摘Paraquat(1,1’-dimethyl-4,4’-bipyridinium dichloride,PQ)has been widely used as a broad spectrum nonselective herbicide in agriculture for decades(Baldwin et al.,1968).Plants absorb PQ from their environment and transport to the chloroplasts,the site of its action where it competes for electrons from photosystem I(PSI)and cyclically generates superoxide that is converted to H2O2by superoxide dismutases(SODs),resultantly accumulating a large amount of reactive oxygen species(ROS)and thereby killing plants(Farrington et al.,1973).
