Most eukaryotes employ a variety of mechanisms to defend the integrity of their genome by recognizing and silencing parasitic mobile nucleic acids.However,recent studies have shown that genomic DNA undergoes extensive...Most eukaryotes employ a variety of mechanisms to defend the integrity of their genome by recognizing and silencing parasitic mobile nucleic acids.However,recent studies have shown that genomic DNA undergoes extensive rearrangements,including DNA elimination,fragmentation,and unscrambling,during the sexual reproduction of ciliated protozoa.Non-coding RNAs have been identified to program and regulate genome rearrangement events.In Paramecium and Tetrahymena,scan RNAs(scnRNAs)are produced from micronuclei and transported to vegetative macronuclei,in which scnRNA elicits the elimination of cognate genomic DNA.In contrast,Piwi-interacting RNAs(piRNAs)in Oxytricha enable the retention of genomic DNA that exhibits sequence complementarity in macronuclei.An RNA interference(RNAi)-like mechanism has been found to direct these genomic rearrangements.Furthermore,in Oxytricha,maternal RNA templates can guide the unscrambling process of genomic DNA.The non-coding RNA-directed genome rearrangements may have profound evolutionary implications,for example,eliciting the multigenerational inheritance of acquired adaptive traits.展开更多
Metalloproteins have inspired chemists for many years to synthesize artificial catalysts that mimic native enzymes.As a complementary approach to studying native enzymes or making synthetic models,biosynthetic approac...Metalloproteins have inspired chemists for many years to synthesize artificial catalysts that mimic native enzymes.As a complementary approach to studying native enzymes or making synthetic models,biosynthetic approach using small and stable proteins to model native enzymes has offered advantages of incorporating non-covalent secondary sphere interactions under physiological conditions.However,most biosynthetic models are restricted to natural amino acids.To overcome this limitation,incorporating unnatural amino acids into the biosynthetic models has shown promises.In this review,we summarize first synthetic,semisynthetic and biological methods of incorporates unnatural amino acids(UAAs)into proteins,followed by progress made in incorporating UAAs into both native metalloproteins and their biosynthetic models to fine-tune functional properties beyond native enzymes or their variants containing natural amino acids,such as reduction potentials of azurin,O_2 reduction rates and percentages of product formation of HCO models in Mb,the rate of radical transport in ribonucleotide reductase(RNR)and the proton and electron transfer pathways in photosystemⅡ(PSⅡ).We also discuss how this endeavour has allowed systematic investigations of precise roles of conserved residues in metalloproteins,such as Metl21 in azurin,Tyr244 that is cross-linked to one of the three His ligands to CuB in HCO,Tyr122,356,730 and 731 in RNR and TyrZ in PSⅡ.These examples have demonstrated that incorporating UAAs has provided a new dimension in our efforts to mimic native enzymes and in providing deeper insights into structural features responsible high enzymatic activity and reaction mechanisms,making it possible to design highly efficient artificial catalysts with similar or even higher activity than native enzymes.展开更多
基金supported by grants from the National Basic Research Program of China(2011CBA01103)the National Natural Science Foundation of China(31171254)the Fundamental Research Funds for Central Universities(WK2060190018)
文摘Most eukaryotes employ a variety of mechanisms to defend the integrity of their genome by recognizing and silencing parasitic mobile nucleic acids.However,recent studies have shown that genomic DNA undergoes extensive rearrangements,including DNA elimination,fragmentation,and unscrambling,during the sexual reproduction of ciliated protozoa.Non-coding RNAs have been identified to program and regulate genome rearrangement events.In Paramecium and Tetrahymena,scan RNAs(scnRNAs)are produced from micronuclei and transported to vegetative macronuclei,in which scnRNA elicits the elimination of cognate genomic DNA.In contrast,Piwi-interacting RNAs(piRNAs)in Oxytricha enable the retention of genomic DNA that exhibits sequence complementarity in macronuclei.An RNA interference(RNAi)-like mechanism has been found to direct these genomic rearrangements.Furthermore,in Oxytricha,maternal RNA templates can guide the unscrambling process of genomic DNA.The non-coding RNA-directed genome rearrangements may have profound evolutionary implications,for example,eliciting the multigenerational inheritance of acquired adaptive traits.
基金supported by the US National Science Foundation(CHE-1413328)the Major State Basic Research Program of China(2015CB856203)+1 种基金the National Natural Science Foundation of China (21325211,31500641)theTianjinMunicipalGrant(13ZCZDSY04800, 14ZCZDSY00059,14JCYBJC43400)
文摘Metalloproteins have inspired chemists for many years to synthesize artificial catalysts that mimic native enzymes.As a complementary approach to studying native enzymes or making synthetic models,biosynthetic approach using small and stable proteins to model native enzymes has offered advantages of incorporating non-covalent secondary sphere interactions under physiological conditions.However,most biosynthetic models are restricted to natural amino acids.To overcome this limitation,incorporating unnatural amino acids into the biosynthetic models has shown promises.In this review,we summarize first synthetic,semisynthetic and biological methods of incorporates unnatural amino acids(UAAs)into proteins,followed by progress made in incorporating UAAs into both native metalloproteins and their biosynthetic models to fine-tune functional properties beyond native enzymes or their variants containing natural amino acids,such as reduction potentials of azurin,O_2 reduction rates and percentages of product formation of HCO models in Mb,the rate of radical transport in ribonucleotide reductase(RNR)and the proton and electron transfer pathways in photosystemⅡ(PSⅡ).We also discuss how this endeavour has allowed systematic investigations of precise roles of conserved residues in metalloproteins,such as Metl21 in azurin,Tyr244 that is cross-linked to one of the three His ligands to CuB in HCO,Tyr122,356,730 and 731 in RNR and TyrZ in PSⅡ.These examples have demonstrated that incorporating UAAs has provided a new dimension in our efforts to mimic native enzymes and in providing deeper insights into structural features responsible high enzymatic activity and reaction mechanisms,making it possible to design highly efficient artificial catalysts with similar or even higher activity than native enzymes.
