CRISPR-Cas technologies have greatly reshaped the biology field.In this review,we discuss the CRISPR-Cas with a particular focus on the associated technologies and applications of CRISPR-Cas9 and CRISPR-Cas12a,which h...CRISPR-Cas technologies have greatly reshaped the biology field.In this review,we discuss the CRISPR-Cas with a particular focus on the associated technologies and applications of CRISPR-Cas9 and CRISPR-Cas12a,which have been most widely studied and used.We discuss the biological mechanisms of CRISPR-Cas as immune defense systems,recently-discovered anti-CRISPR-Cas systems,and the emerging Cas variants(such as xCas9 and Cas13)with unique characteristics.Then,we highlight various CRISPR-Cas biotechnologies,including nucleasedependent genome editing,CRISPR gene regulation(including CRISPR interference/activation),DNA/RNA base editing,and nucleic acid detection.Last,we summarize up-to-date applications of the biotechnologies for synthetic biology and metabolic engineering in various bacterial species.展开更多
Cas1 is a key component of the CRISPR adaptation complex,which captures and integrates foreign DNA into the CRISPR array,resulting in the generation of new spacers.We have determined crystal structures of Thermus ther...Cas1 is a key component of the CRISPR adaptation complex,which captures and integrates foreign DNA into the CRISPR array,resulting in the generation of new spacers.We have determined crystal structures of Thermus thermophilus Cas1 involved in new spacer acquisition both in complex with branched DNA and in the free state.Cas1 forms an asymmetric dimer without DNA.Conversely,two asymmetrical dimers bound to two branched DNAs result in the formation of a DNA-mediated tetramer,dimer of structurally asymmetrical dimers,in which the two subunits markedly present different conformations.In the DNA binding complex,the N-terminal domain adopts different orientations with respect to the C-terminal domain in the two monomers that form the dimer.Substrate binding triggers a conformational change in the loop 164–177 segment.This loop is also involved in the 3′fork arm and 5′fork arm strand recognition in monomer A and B,respectively.This study provides important insights into the molecular mechanism of new spacer adaptation.展开更多
Social dysfunction is a risk factor for several neuropsychiatric illnesses.Previous studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social behaviors.Howeve r,the role ...Social dysfunction is a risk factor for several neuropsychiatric illnesses.Previous studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social behaviors.Howeve r,the role of the connections between the LS and its downstream brain regions in social behavio rs remains unclea r.In this study,we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1(vCA1)influence sociability.Our res ults showed that gamma-aminobutyric acid(GABA)-e rgic neuro ns were activated following social experience,and that social behavio rs were enhanced by chemogenetic modulation of these neurons.Moreover,LS GABAergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons,and regulating LSGABA→vCA1Gluneural projections affected social behaviors,which were impeded by suppressing LSprojecting vCA1 neuronal activity or inhibiting GABAAreceptors in vCA1.These findings support the hypothesis that LS inputs to the vCA1 can control social prefe rences and social novelty behaviors.These findings provide new insights rega rding the neural circuits that regulate sociability.展开更多
蛋白磷酸酶是一组在人类细胞中广泛存在并催化已经磷酸化的蛋白质分子发生去磷酸化反应的一类酶分子。而磷酸蛋白磷酸酶催化亚基超家族是一组主要使丝氨酸/苏氨酸残基去磷酸化的蛋白磷酸酶,其中蛋白磷酸酶1(protein phosphatase-1,PP1)...蛋白磷酸酶是一组在人类细胞中广泛存在并催化已经磷酸化的蛋白质分子发生去磷酸化反应的一类酶分子。而磷酸蛋白磷酸酶催化亚基超家族是一组主要使丝氨酸/苏氨酸残基去磷酸化的蛋白磷酸酶,其中蛋白磷酸酶1(protein phosphatase-1,PP1)参与了真核生物大部分的去磷酸化反应,并参与调节多种生物活动。由PPP1CA基因编码的PP1催化亚基α(catalytic subunit alpha of protein phosphatase-1,PP1A)是修饰PP1最重要的一种亚型,在多种肿瘤生存和转移中起着重要作用,但其在肿瘤中也会表现出抑制作用,这使其可能成为肿瘤治疗的新靶标。因此,本文旨在对PP1A在多种肿瘤中关键作用进行综述,并针对其作为肿瘤治疗的新靶标潜力进行评价。展开更多
基金Natural Science Foundation of Shanghai(Grant No.18ZR1420500)the Science and Technology Commission of Shanghai Municipality(Grant No.18JC1413600).Y.X.acknowledges National 1000 Youth Talents Program.W.L.and Y.Z.are recipients of China Postdoctoral Science Foundation(2018M632119 and 2018M632098).
文摘CRISPR-Cas technologies have greatly reshaped the biology field.In this review,we discuss the CRISPR-Cas with a particular focus on the associated technologies and applications of CRISPR-Cas9 and CRISPR-Cas12a,which have been most widely studied and used.We discuss the biological mechanisms of CRISPR-Cas as immune defense systems,recently-discovered anti-CRISPR-Cas systems,and the emerging Cas variants(such as xCas9 and Cas13)with unique characteristics.Then,we highlight various CRISPR-Cas biotechnologies,including nucleasedependent genome editing,CRISPR gene regulation(including CRISPR interference/activation),DNA/RNA base editing,and nucleic acid detection.Last,we summarize up-to-date applications of the biotechnologies for synthetic biology and metabolic engineering in various bacterial species.
基金The research was funded by the National Natural Science Foundation of China(31630015,31725008)the Chinese Academy of Sciences(QYZDY-SSW-SMC021).
文摘Cas1 is a key component of the CRISPR adaptation complex,which captures and integrates foreign DNA into the CRISPR array,resulting in the generation of new spacers.We have determined crystal structures of Thermus thermophilus Cas1 involved in new spacer acquisition both in complex with branched DNA and in the free state.Cas1 forms an asymmetric dimer without DNA.Conversely,two asymmetrical dimers bound to two branched DNAs result in the formation of a DNA-mediated tetramer,dimer of structurally asymmetrical dimers,in which the two subunits markedly present different conformations.In the DNA binding complex,the N-terminal domain adopts different orientations with respect to the C-terminal domain in the two monomers that form the dimer.Substrate binding triggers a conformational change in the loop 164–177 segment.This loop is also involved in the 3′fork arm and 5′fork arm strand recognition in monomer A and B,respectively.This study provides important insights into the molecular mechanism of new spacer adaptation.
基金supported by the National Natural Science Foundation of China,No.82171521(to CL)the Special Funds ofTaishan Scholars Project of Shandong Province,No.tsqn202211368(to CL)+2 种基金the Natural Science Foundation of Shandong Province,Nos.ZR2022YQ65(to CL),ZR2021MH073(to CL),ZR2019PH109(to WW)the Projects of Medical and Health Technology Development Program in Shandong Province,China,Nos.202003090720(to DZ),202003070728(to JL),2019 WS329(to DW)the Scientific Research Foundation of Binzhou Medical University,No.BY2018KJ21(to DW)。
文摘Social dysfunction is a risk factor for several neuropsychiatric illnesses.Previous studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social behaviors.Howeve r,the role of the connections between the LS and its downstream brain regions in social behavio rs remains unclea r.In this study,we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1(vCA1)influence sociability.Our res ults showed that gamma-aminobutyric acid(GABA)-e rgic neuro ns were activated following social experience,and that social behavio rs were enhanced by chemogenetic modulation of these neurons.Moreover,LS GABAergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons,and regulating LSGABA→vCA1Gluneural projections affected social behaviors,which were impeded by suppressing LSprojecting vCA1 neuronal activity or inhibiting GABAAreceptors in vCA1.These findings support the hypothesis that LS inputs to the vCA1 can control social prefe rences and social novelty behaviors.These findings provide new insights rega rding the neural circuits that regulate sociability.
文摘蛋白磷酸酶是一组在人类细胞中广泛存在并催化已经磷酸化的蛋白质分子发生去磷酸化反应的一类酶分子。而磷酸蛋白磷酸酶催化亚基超家族是一组主要使丝氨酸/苏氨酸残基去磷酸化的蛋白磷酸酶,其中蛋白磷酸酶1(protein phosphatase-1,PP1)参与了真核生物大部分的去磷酸化反应,并参与调节多种生物活动。由PPP1CA基因编码的PP1催化亚基α(catalytic subunit alpha of protein phosphatase-1,PP1A)是修饰PP1最重要的一种亚型,在多种肿瘤生存和转移中起着重要作用,但其在肿瘤中也会表现出抑制作用,这使其可能成为肿瘤治疗的新靶标。因此,本文旨在对PP1A在多种肿瘤中关键作用进行综述,并针对其作为肿瘤治疗的新靶标潜力进行评价。
