Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human dise...Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.展开更多
In eukaryotes,microtubule polymers are essential for cellular plasticity and fate decisions.End-binding(EB)proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dyna...In eukaryotes,microtubule polymers are essential for cellular plasticity and fate decisions.End-binding(EB)proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in mitosis.Here,we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid–liquid phase separation to compartmentalize the kinetochore–microtubule plus-end machinery,ensuring accurate kinetochore–microtubule interactions during chromosome segregation in mitosis.Perturbation of EB1–TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila embryos.Lys220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis,and persistent acetylation at Lys220 attenuates phase separation of the EB1-mediated complex,dissolves droplets in vitro,and harnesses accurate chromosome segregation.Our data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis.展开更多
Dear Editor,Protein histidine methylation has been found to be a widespread post-translational modification(PTM)in mammalian cells and represents more than 13%of all protein methylation events in the human methylome(N...Dear Editor,Protein histidine methylation has been found to be a widespread post-translational modification(PTM)in mammalian cells and represents more than 13%of all protein methylation events in the human methylome(Ning et al.,2016;Kapell and Jakobsson,2021).Recently,we and other groups independently identified METTL9 as the first broad-specificity histidine N1 methyltransferase in mammals(Davydova et al.,2021;Lv et al.,2021).METTL9 methylates a variety of substrates with a common x-His-x-His motif(His is for histidine;the second x is preferably small amino acids:A/C/G/S)and catalyzes methyl transfer to the last histidine.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
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
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
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
Transcription factors(TFs)regulate cellular activities by controlling gene expression,but a predictive model describing how TFs quantitatively modulate human transcriptomes is lacking.We construct a universal human ge...Transcription factors(TFs)regulate cellular activities by controlling gene expression,but a predictive model describing how TFs quantitatively modulate human transcriptomes is lacking.We construct a universal human gene expression predictor named EXPLICIT-Human and utilize it to decode transcriptional regulation.Using the expression of 1613 TFs,the predictor reconstitutes highly accurate transcriptomes for samples derived from a wide range of tissues and conditions.The broad applicability of the predictor indicates that it recapitulates the quantitative relationships between TFs and target genes ubiquitous across tissues.Significant interacting TF-target gene pairs are extracted from the predictor and enable downstream inference of TF regulators for diverse pathways involved in development,immunity,metabolism,and stress response.A detailed analysis of the hematopoiesis process reveals an atlas of key TFs regulating the development of different hematopoietic cell lineages,and a portion of these TFs are conserved between humans and mice.The results demonstrate that our method is capable of delineating the TFs responsible for fate determination.Compared to other existing tools,EXPLICIT-Human shows a better performance in recovering the correct TF regulators.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
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
Dear Editor Clathrin-mediated endocytosis （CME） is an evolutionary conserved mechanism by which plasma membrane （PM）-based cargo proteins are recognized by adaptor protein complexes and internalized. Apart from th...Dear Editor Clathrin-mediated endocytosis （CME） is an evolutionary conserved mechanism by which plasma membrane （PM）-based cargo proteins are recognized by adaptor protein complexes and internalized. Apart from the canonical adaptor complex, AP-2, plant cells rely on the TPLATE complex （TPC） to execute CME （Gadeyne et al., 2014）. FT160100218, DP110100410）, the Ministry of Education, Culture, Sports, Science, and Technology of Japan （24114003, 15H04382, and 17K19412）, the European Research Council （ERC grant 682436）, the IRRTF-RNC （no. 501892） and a USA National Science Foundation CAREER Award.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
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
Study of cell-in-cell phenomena began with the desire to understand the complex phenotype, which stemmed from Lewis＇ observation ofnon-phagocytotic process of cell-eating-cell in 1925. Humble et al. coined the term ...Study of cell-in-cell phenomena began with the desire to understand the complex phenotype, which stemmed from Lewis＇ observation ofnon-phagocytotic process of cell-eating-cell in 1925. Humble et al. coined the term ＂emperipolesis＂ （from the Greek, wandering round about within） in 1950s, to define the heterogeneous cell-in-cell phenomena when they studied bio- logical interaction of lymphocytes with other cells . Emperipolesis has since been found to be commonly enacted by lymphocytes in physiological and pathophysiological settings . Since the term ＂emperipolesis＂ was annotated, a challenge has been set to understand how a cell inhabits in the other, what are their respective fates, and the biological relevance of co-habitation.展开更多
Visualization of specific molecules and their interactions in real space and time is essential to delineate how cellular plasticity and dynamics are achieved and orchestrated as perturba- tion of cellular plasticity a...Visualization of specific molecules and their interactions in real space and time is essential to delineate how cellular plasticity and dynamics are achieved and orchestrated as perturba- tion of cellular plasticity and dynamics is detrimental to health. Elucidation of cellular dynamics requires molecular imaging at nanometer scale at millisecond resolution. The 1 st International Conference on Cellular Dynamics and Chemical Biology held in Hefei, China （from 12 September to 15 September, 2008） launched the quest by bringing synergism among photonics, chemistry and biology.展开更多
In the fission yeast Schizosaccharomyces pombe,Mei2,an RNA-binding protein essential for entry into meiosis,regulates meiosis initiation.Mei2 binds to a specific non-coding RNA species,meiRNA,and accumulates at the sm...In the fission yeast Schizosaccharomyces pombe,Mei2,an RNA-binding protein essential for entry into meiosis,regulates meiosis initiation.Mei2 binds to a specific non-coding RNA species,meiRNA,and accumulates at the sme2 gene locus,which encodes meiRNA.Previous research has shown that the Mei2 C-terminal RNA recognition motif(RRM3)physically interacts with the meiRNA 5'region in vitro and stimulates meiosis in vivo.However,the underlying mechanisms still remain elusive.We first employed an in vitro crosslinking and immunoprecipitation sequencing(CLIP-seq)assay and demonstrated a preference for U-rich motifs of meiRNA by Mei2 RRM3.We then solved the crystal structures of Mei2 RRM3 in the apo form and complex with an 8 mer RNA fragment,derived from meiRNA,as detected by in vitro CLIP-seq.These results provide structural insights into the Mei2 RRM3-meiRNA complex and reveal that Mei2 RRM3 binds specifically to the Uuc(U)sequence.Furthermore,a structure-based Mei2 mutation,Mei2F644A causes defective karyogamy,suggesting an essential role of the RNA-binding ability of Mei2 in regulating meiosis.展开更多
Considerable developments have been observed in fragment-based lead/drug discovery(FBLD/FBDD)recently,with four drugs approved and many others under investigation.Nuclear magnetic resonance(NMR)has gained increasing p...Considerable developments have been observed in fragment-based lead/drug discovery(FBLD/FBDD)recently,with four drugs approved and many others under investigation.Nuclear magnetic resonance(NMR)has gained increasing popularity in FBLD due to its intrinsic capability in characterizing protein-ligand interactions in a large dynamic range of affinity,from weak hits to highly potent drugs.Here,we summarize NMR applications in fragment-based hit-to-lead evolution,including the construction of a fragment library,screening methods,spectra processing,and the delineation of the protein-ligand binding modes.These state-of-the-art NMR techniques have been exemplified in the discovery of inhibitors against multiple targets over the past five years,and they are expected to continue to provide new insights in the future.展开更多
Microtubules grow not only from the centrosome but also from various noncentrosomal microtubule-organizing centers(MTOCs),including the nuclear envelope(NE)and pre-existing microtubules.The evolutionarily conserved pr...Microtubules grow not only from the centrosome but also from various noncentrosomal microtubule-organizing centers(MTOCs),including the nuclear envelope(NE)and pre-existing microtubules.The evolutionarily conserved proteins Mtol/CDK5RAP2 and Alpl4/TOG/XMAP215 have been shown to be involved in promoting microtubule nucleation.However,it has remained elusive as to how the microtubule nucleation promoting factors are specified to various noncentrosomal MTOCs,particularly the NE,and how these proteins coordinate to organize microtubule assembly.Here,we demonstrate that in the fission yeast Schizosaccharomyces pombe,efficient interphase microtubule growth from the NE requires Alp7/TACC,Alpl4/TOG/XMAP215,and Mtol/CDK5RAP2.The absence of Alp7,A lp l4 t or Mtol compromises microtubule regrowth on the NE in cells undergoing microtubule repolymerization.We further demonstrate that Alp7 and Mtol interdependently localize to the NE in cells without microtubules and that A lp l4 localizes to the NE in an Alp7 and Mtol-dependent manner.Tethering Mtol to the NE in cells lacking Alp7 partially restores microtubule number and the efficiency of microtubule generation from the NE.Hence,our study delineates that Alp7,A lpl4,and Mtol work in concert to regulate interphase microtubule regrowth on the NE.展开更多
Spatial regulation of microtubule catastrophe is important for controlling microtubule length and consequently contributes to the proper establishment of cell polarity and cell growth.The+TIP proteins including Tipl/C...Spatial regulation of microtubule catastrophe is important for controlling microtubule length and consequently contributes to the proper establishment of cell polarity and cell growth.The+TIP proteins including Tipl/CLIP-170,Klp5/Kinesin-8,and Alpl4/XMAP215 reside at microtubule plus ends to regulate microtubule dynamics.In the fission yeast Schizosaccharomyces pombe,Tipi and Alpl4 serve as microtubule-stabilizing factors,while Klp5 functions oppositely as a catastrophe-promoting factor.Despite that Tipi has been shown to play a key role in restricting microtubule catastrophe to the cell end,how Tipi fulfills the role remains to be determined.Employing live-cell microscopy,we showed that the absence of Tip i impairs the localization of both Klp5 and Alpl4 at microtubule plus ends,but the absence of Klp5 prolongs the residence time of Tipi at microtubule plus ends.We further revealed that Klp5 accumulates behind Tip i at microtubule plus ends in a Tipl-dependent manner.In addition,artificially tethering Klp5 to microtubule plus ends promotes premature microtubule catastrophe,while tethering Alpl4 to microtubule plus ends in the cells lacking Tipi rescues the phenotype of short microtubules.These findings establish that Tipi restricts microtubule catastrophe to the cell end likely by spatially restricting the microtubule catastrophe activity of Klp5 and stabilizing Alpl4 at microtubule plus ends.Thus,the work demonstrates the orchestration of Tipi,Alpl4,and Klp5 in ensuring microtubule catastrophe at the cell end.展开更多
Dietary restriction usually suppresses biosynthesis but activates catabolic pathways in animals.However,the short-term starvation enhances biosynthetic activities and promotes ribosomal biogenesis in adult Caenorhabdi...Dietary restriction usually suppresses biosynthesis but activates catabolic pathways in animals.However,the short-term starvation enhances biosynthetic activities and promotes ribosomal biogenesis in adult Caenorhabditis elegans.The mechanism underlying the processes remains largely unknown.Here,we find that the short-term starvation enhances the SL1 trans-splicing of translation-related genes in adult C.elegans by transcriptome analysis.The small nuclear RNA-activating protein complex(SNAPc)promotes SL RNA production and mediates starvation-induced trans-splicing.TOFU-5,a core factor in the upstream sequence transcription complex(USTC)essential for piRNA production,is also involved in the starvationinduced trans-splicing processes.Knocking down components of the SNAPc complex and tofu-5 extends worm survival under starvation conditions.Taken together,our study highlights the importance of SL transsplicing in the nutrition response and reveals a mechanism of the survival regulation by food deprivation via SNAPc and TOFU-5.展开更多
基金supported by the National Natural Science Foundation of China(31871380,32000500,32070730,32170756,32170804,81330008,81671377,81725010,81725010,81872874,81921006,81922027,81971312,81991512,82030041,82103167,82122024,82125009,82125011,82130044,91749126,91949101,91949207,92049302)the National Key Research and Development Program of China(2017YFA0506400,2018YFA0800200,2018YFA0800700,2018YFA0900200,2018YFC2000100,2018YFC2000400,2018YFE-0203700,20192ACB70002,2019YFA0802202,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002800,2020YFC-2002900,2021ZD0202401)+11 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010100,XDA16010603,XDA16020400,XDB29020000,XDB39000000,XDB39000000,XDB39030300)the China Association for Science and Technology(2021QNRC001)the Beijing Municipal Science and Technology Commission(Z200022)the Natural Science Foundation of Shanghai(21JC1406400)the Key Programs of the Jiangxi ProvinceChina(20192ACB70002)the“Shu Guang”Project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation(19SG18)the Shanghai Sailing Program(22YF1434300)the Research Project of Joint Laboratory of University of Science and Technology of China and Anhui Mental Health Center(2019LH03)the Fundamental Research Funds for the Central Universities(WK2070210004)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(YESS20210002)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2022083)。
文摘Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.
基金supported by grants from the National Key Research and Development Program of China(2022YFA1303100,2022YFA0806800,2022YFA1302700,and 2017YFA0503600)the National Natural Science Foundation of China(32090040,92153302,92254302,92253305,31621002,21922706,92059102,and 92253301)+1 种基金the Plans for Major Provincial Science&Technology Projects of Anhui Province(202303a0702003),the Ministry of Education(IRT_17R102)the Fundamental Research Funds for the Central Universities(KB9100000007 and KB9100000013).
文摘In eukaryotes,microtubule polymers are essential for cellular plasticity and fate decisions.End-binding(EB)proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in mitosis.Here,we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid–liquid phase separation to compartmentalize the kinetochore–microtubule plus-end machinery,ensuring accurate kinetochore–microtubule interactions during chromosome segregation in mitosis.Perturbation of EB1–TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila embryos.Lys220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis,and persistent acetylation at Lys220 attenuates phase separation of the EB1-mediated complex,dissolves droplets in vitro,and harnesses accurate chromosome segregation.Our data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis.
基金supported by NSFC Grant No.81872327(to WP),"USTC Important Direction"Cultivation Project(WK3520000013)(to WP)"The Fundamental Research Funds for the Central Universities"(WK9110000065)(to DC)"The Fundamental Research Funds of USTC"(2019ZC027)(to DC).
文摘Dear Editor,Protein histidine methylation has been found to be a widespread post-translational modification(PTM)in mammalian cells and represents more than 13%of all protein methylation events in the human methylome(Ning et al.,2016;Kapell and Jakobsson,2021).Recently,we and other groups independently identified METTL9 as the first broad-specificity histidine N1 methyltransferase in mammals(Davydova et al.,2021;Lv et al.,2021).METTL9 methylates a variety of substrates with a common x-His-x-His motif(His is for histidine;the second x is preferably small amino acids:A/C/G/S)and catalyzes methyl transfer to the last histidine.
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 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 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Transcription factors(TFs)regulate cellular activities by controlling gene expression,but a predictive model describing how TFs quantitatively modulate human transcriptomes is lacking.We construct a universal human gene expression predictor named EXPLICIT-Human and utilize it to decode transcriptional regulation.Using the expression of 1613 TFs,the predictor reconstitutes highly accurate transcriptomes for samples derived from a wide range of tissues and conditions.The broad applicability of the predictor indicates that it recapitulates the quantitative relationships between TFs and target genes ubiquitous across tissues.Significant interacting TF-target gene pairs are extracted from the predictor and enable downstream inference of TF regulators for diverse pathways involved in development,immunity,metabolism,and stress response.A detailed analysis of the hematopoiesis process reveals an atlas of key TFs regulating the development of different hematopoietic cell lineages,and a portion of these TFs are conserved between humans and mice.The results demonstrate that our method is capable of delineating the TFs responsible for fate determination.Compared to other existing tools,EXPLICIT-Human shows a better performance in recovering the correct TF regulators.
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This work was supported by the Max-Planck Gesellschaft, the Deutsche Forschungsgemeinschaft, the National Natural Science Foundation of China （grants 31530051）, the Swiss Federal Institute of Technology of Zurich （ETH-Z）, the Swiss National Foundation （SNF 2-77212-15）, the University of Melbourne, the Australian Research Council （CE1101007,
文摘Dear Editor Clathrin-mediated endocytosis （CME） is an evolutionary conserved mechanism by which plasma membrane （PM）-based cargo proteins are recognized by adaptor protein complexes and internalized. Apart from the canonical adaptor complex, AP-2, plant cells rely on the TPLATE complex （TPC） to execute CME （Gadeyne et al., 2014）. FT160100218, DP110100410）, the Ministry of Education, Culture, Sports, Science, and Technology of Japan （24114003, 15H04382, and 17K19412）, the European Research Council （ERC grant 682436）, the IRRTF-RNC （no. 501892） and a USA National Science Foundation CAREER Award.
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).
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.
文摘Study of cell-in-cell phenomena began with the desire to understand the complex phenotype, which stemmed from Lewis＇ observation ofnon-phagocytotic process of cell-eating-cell in 1925. Humble et al. coined the term ＂emperipolesis＂ （from the Greek, wandering round about within） in 1950s, to define the heterogeneous cell-in-cell phenomena when they studied bio- logical interaction of lymphocytes with other cells . Emperipolesis has since been found to be commonly enacted by lymphocytes in physiological and pathophysiological settings . Since the term ＂emperipolesis＂ was annotated, a challenge has been set to understand how a cell inhabits in the other, what are their respective fates, and the biological relevance of co-habitation.
文摘Visualization of specific molecules and their interactions in real space and time is essential to delineate how cellular plasticity and dynamics are achieved and orchestrated as perturba- tion of cellular plasticity and dynamics is detrimental to health. Elucidation of cellular dynamics requires molecular imaging at nanometer scale at millisecond resolution. The 1 st International Conference on Cellular Dynamics and Chemical Biology held in Hefei, China （from 12 September to 15 September, 2008） launched the quest by bringing synergism among photonics, chemistry and biology.
基金This work was financially supported by grants from the Ministry of Science and Technology of China(2019YFA0508403)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39010300)+2 种基金the National Natural Science Foundation of China(32090040,31870760,32171222,92149302,U1932122,and 32100958)the China Postdoctoral Science Foundation(2019M662182)the Fundamental Research Funds for the Central Universities(WK2340000097).
文摘In the fission yeast Schizosaccharomyces pombe,Mei2,an RNA-binding protein essential for entry into meiosis,regulates meiosis initiation.Mei2 binds to a specific non-coding RNA species,meiRNA,and accumulates at the sme2 gene locus,which encodes meiRNA.Previous research has shown that the Mei2 C-terminal RNA recognition motif(RRM3)physically interacts with the meiRNA 5'region in vitro and stimulates meiosis in vivo.However,the underlying mechanisms still remain elusive.We first employed an in vitro crosslinking and immunoprecipitation sequencing(CLIP-seq)assay and demonstrated a preference for U-rich motifs of meiRNA by Mei2 RRM3.We then solved the crystal structures of Mei2 RRM3 in the apo form and complex with an 8 mer RNA fragment,derived from meiRNA,as detected by in vitro CLIP-seq.These results provide structural insights into the Mei2 RRM3-meiRNA complex and reveal that Mei2 RRM3 binds specifically to the Uuc(U)sequence.Furthermore,a structure-based Mei2 mutation,Mei2F644A causes defective karyogamy,suggesting an essential role of the RNA-binding ability of Mei2 in regulating meiosis.
基金We thank the Ministry of Science and Technology of China(2019YFA0508400 and 2016YFA0500700)the National Natural Science Foundation of China(21874123 and 21807095)Collaborative Innovation Program of Hefei Science Center,CAS(2020HSC-CIP009)for the financial support.
文摘Considerable developments have been observed in fragment-based lead/drug discovery(FBLD/FBDD)recently,with four drugs approved and many others under investigation.Nuclear magnetic resonance(NMR)has gained increasing popularity in FBLD due to its intrinsic capability in characterizing protein-ligand interactions in a large dynamic range of affinity,from weak hits to highly potent drugs.Here,we summarize NMR applications in fragment-based hit-to-lead evolution,including the construction of a fragment library,screening methods,spectra processing,and the delineation of the protein-ligand binding modes.These state-of-the-art NMR techniques have been exemplified in the discovery of inhibitors against multiple targets over the past five years,and they are expected to continue to provide new insights in the future.
基金the National Key Research and Development Program of China(2017YFA0503600)the National Natural Science Foundation of China(91754106,31871350,31671406,31601095,and 31621002)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19040101)the Major/lnnovative Program of Development Foundation of Hefei Center for Physical Science and Technology(2017FXCX008)China’s 1000 Young Talents Recruitment Program.
文摘Microtubules grow not only from the centrosome but also from various noncentrosomal microtubule-organizing centers(MTOCs),including the nuclear envelope(NE)and pre-existing microtubules.The evolutionarily conserved proteins Mtol/CDK5RAP2 and Alpl4/TOG/XMAP215 have been shown to be involved in promoting microtubule nucleation.However,it has remained elusive as to how the microtubule nucleation promoting factors are specified to various noncentrosomal MTOCs,particularly the NE,and how these proteins coordinate to organize microtubule assembly.Here,we demonstrate that in the fission yeast Schizosaccharomyces pombe,efficient interphase microtubule growth from the NE requires Alp7/TACC,Alpl4/TOG/XMAP215,and Mtol/CDK5RAP2.The absence of Alp7,A lp l4 t or Mtol compromises microtubule regrowth on the NE in cells undergoing microtubule repolymerization.We further demonstrate that Alp7 and Mtol interdependently localize to the NE in cells without microtubules and that A lp l4 localizes to the NE in an Alp7 and Mtol-dependent manner.Tethering Mtol to the NE in cells lacking Alp7 partially restores microtubule number and the efficiency of microtubule generation from the NE.Hence,our study delineates that Alp7,A lpl4,and Mtol work in concert to regulate interphase microtubule regrowth on the NE.
基金the National Key Research and Development Program of China(2018YFC1004700)the National Natural Science Foundation of China(91754106,31671406,31871350,and 31601095)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB190A0101)the Major/lnnovative Program of Development Foundation of Hefei Center for Physical Science and Technology(2017FXCX008)China’s 1000 Young Talents Recruitment Program.
文摘Spatial regulation of microtubule catastrophe is important for controlling microtubule length and consequently contributes to the proper establishment of cell polarity and cell growth.The+TIP proteins including Tipl/CLIP-170,Klp5/Kinesin-8,and Alpl4/XMAP215 reside at microtubule plus ends to regulate microtubule dynamics.In the fission yeast Schizosaccharomyces pombe,Tipi and Alpl4 serve as microtubule-stabilizing factors,while Klp5 functions oppositely as a catastrophe-promoting factor.Despite that Tipi has been shown to play a key role in restricting microtubule catastrophe to the cell end,how Tipi fulfills the role remains to be determined.Employing live-cell microscopy,we showed that the absence of Tip i impairs the localization of both Klp5 and Alpl4 at microtubule plus ends,but the absence of Klp5 prolongs the residence time of Tipi at microtubule plus ends.We further revealed that Klp5 accumulates behind Tip i at microtubule plus ends in a Tipl-dependent manner.In addition,artificially tethering Klp5 to microtubule plus ends promotes premature microtubule catastrophe,while tethering Alpl4 to microtubule plus ends in the cells lacking Tipi rescues the phenotype of short microtubules.These findings establish that Tipi restricts microtubule catastrophe to the cell end likely by spatially restricting the microtubule catastrophe activity of Klp5 and stabilizing Alpl4 at microtubule plus ends.Thus,the work demonstrates the orchestration of Tipi,Alpl4,and Klp5 in ensuring microtubule catastrophe at the cell end.
基金supported by grants from the National Key R&D Program of China (2019YFA0802600)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB39010600)+3 种基金the National Natural Science Foundation of China (91940303, 31870812, 32070619, 31871300 and 31900434)the China Postdoctoral Science Foundation (2018M632542)the Anhui Natural Science Foundation (1808085QC82 and 1908085QC96)supported in part by the Fundamental Research Funds for the Central Universities.
文摘Dietary restriction usually suppresses biosynthesis but activates catabolic pathways in animals.However,the short-term starvation enhances biosynthetic activities and promotes ribosomal biogenesis in adult Caenorhabditis elegans.The mechanism underlying the processes remains largely unknown.Here,we find that the short-term starvation enhances the SL1 trans-splicing of translation-related genes in adult C.elegans by transcriptome analysis.The small nuclear RNA-activating protein complex(SNAPc)promotes SL RNA production and mediates starvation-induced trans-splicing.TOFU-5,a core factor in the upstream sequence transcription complex(USTC)essential for piRNA production,is also involved in the starvationinduced trans-splicing processes.Knocking down components of the SNAPc complex and tofu-5 extends worm survival under starvation conditions.Taken together,our study highlights the importance of SL transsplicing in the nutrition response and reveals a mechanism of the survival regulation by food deprivation via SNAPc and TOFU-5.
