Selenium (Se) is a trace element required for normal body function. Its supplementation of human diet at standard optimum amount prevents oxidative damages in cells and could be a viable method in the prevention of di...Selenium (Se) is a trace element required for normal body function. Its supplementation of human diet at standard optimum amount prevents oxidative damages in cells and could be a viable method in the prevention of diseases related to DNA damage, including cancer, neurodegenerative diseases and aging. While Se anticancer properties have been linked to its ability to remove excess Reactive Oxygen Species (ROS) in cells, the underlying molecular mechanism remains unknown. Recent studies have shown that the removal of ROS alone cannot account for Se anticancer properties. To really comprehend the molecular basis of Se anticancer properties, current researches now focus on the metabolism of Se in the cell, especially Se-containing amino acids. Selenocysteine (Sec) is a novel amino acid and one of the selenium-containing compounds in the cell. It is essential in the maintenance of the integrity of its parent proteins, some of which include enzymes such as Glutathione Peroxidases (GPXs) and Thioredoxin Reductases (TrXs). We propose in this study that the overproduction of Sec via the overexpression of Selenocysteine synthase (SecS) gene and Se supplementation induced cell death in Prostate Carcinoma (PC-3) cells. Although the mechanism underlying the cell death induction is unknown, we propose it could be due to the random incorporation of Sec into proteins at high concentration, causing premature protein degradation and cell death. The outcome of this study showed that increasing the concentration of intracellular Se-containing amino acids may provide important clinical implications for the treatment of cancer.展开更多
Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. This aminoacid is cotranslationally i...Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. This aminoacid is cotranslationally incorporated at UGA codons which usually act as translation stop codons. In eukaryotes, decoding of selenocysteine necessitates the participation of the selenocysteine insertion sequence (SECIS), an element lying in the 3' -untranslated region of selenoprotein mRNAs. A detailed experimental study of the secondary structures of the SECIS elements of rat and human type 1 iodothyronine deiodinases and rat glutathione peroxidase was performed. Enzymatic and chemical structure probing led us to propose a secondary structure model, supported by sequence comparison of 23 SECIS mRNAs. The secondary structure model revealed the existence of a novel type of RNA motif composed of four consecutive non-Watson-Crick base-pairs. Using gel shift experiments, we identified in several mammalian cell type extracts the protein SBP,for SECIS-binding protein, that specifically recognizes the iodothyronine deiodinases and glutathione peroxidase SECIS elements. The structural model that we derived for the SECIS RNAs discloses RNA features possibly implicated in the binding of SBP and/or SECIS function展开更多
Selenocysteine methyltransferase(SMT)is a key enzyme involved in the Se metabolism pathway,and it is responsible for the catalysis of Se-methylselenocysteine(SeMSC)compound formation.Previous studies showed that selen...Selenocysteine methyltransferase(SMT)is a key enzyme involved in the Se metabolism pathway,and it is responsible for the catalysis of Se-methylselenocysteine(SeMSC)compound formation.Previous studies showed that selenium treatment activated SMT expression and promoted the accumulation of glucosinolates(GSLs)and sulforaphane,but the roles and functional mechanisms of SMT in mediating GSLs and sulforaphane synthesis remain unclear.In this study,we identified the BoSMT gene in broccoli and uncovered its roles in mediating GSLs biosynthesis.Transgenic assays revealed that BoSMT is involved in SeMSC biosynthesis in broccoli.More importantly,the contents of GSLs and sulforaphane were significantly increased in the BoSMT-overexpressing broccoli lines but decreased in the knockdown lines,suggesting that BoSMT played a positive role in regulating GSLs and sulforaphane synthesis.Further evidence indicated that BoSMT-mediated overaccumulation of GSLs and sulforaphane might be due to the increase in the endogenous SeMSC content.Compared with the mock(water)treatment,selenite-induced significantly increases of the SeMSC content in the BoSMT-knockdown plants partially compensated the phenotype of GSLs and sulforaphane loss.Compared with the mock treatment,exogenous SeMSC treatment significantly increased the contents of GSL and sulforaphane and activated GSL synthesis-related gene expression,suggesting that SeMSC acted as a positive regulator for GSL and sulforaphane production.Our findings provided novel insights into selenium-mediated GSLs and sulforaphane accumulation.The genetic manipulation of BoSMT might be a useful strategy for improving the dietary nutritional values of broccoli.展开更多
Anther dehiscence controls optimal interaction between pollen and stigma,thereby determining the successful sexual reproduction.The regulators or mechanisms of this process remain elusive.Here,two CRISPR/Cas9 mutants ...Anther dehiscence controls optimal interaction between pollen and stigma,thereby determining the successful sexual reproduction.The regulators or mechanisms of this process remain elusive.Here,two CRISPR/Cas9 mutants of a rice exocyst subunit gene SEC3A,sec3a-1 and sec3a-2,showed anther indehiscence at anthesis and male sterility at maturity.Pollen viability and germination in the mutants were partly defective,whereas their female gametes undergone a normal development.Hybrid or self-pollinated seeds could be produced by artificial pollination,suggesting potential use of a weak sec3a mutant as a female line during hybrid breeding.SEC3A is widely expressed in various tissues,including anther walls.Further results showed an excessive IAA accumulation and no endothecium lignification in sec3a-1/2 anthers.Our findings suggest that SEC3A appears to regulate anther dehiscence by modulating auxin signaling,providing insights into regulation of anther dehiscence and function of exocyst in plants.展开更多
文摘Selenium (Se) is a trace element required for normal body function. Its supplementation of human diet at standard optimum amount prevents oxidative damages in cells and could be a viable method in the prevention of diseases related to DNA damage, including cancer, neurodegenerative diseases and aging. While Se anticancer properties have been linked to its ability to remove excess Reactive Oxygen Species (ROS) in cells, the underlying molecular mechanism remains unknown. Recent studies have shown that the removal of ROS alone cannot account for Se anticancer properties. To really comprehend the molecular basis of Se anticancer properties, current researches now focus on the metabolism of Se in the cell, especially Se-containing amino acids. Selenocysteine (Sec) is a novel amino acid and one of the selenium-containing compounds in the cell. It is essential in the maintenance of the integrity of its parent proteins, some of which include enzymes such as Glutathione Peroxidases (GPXs) and Thioredoxin Reductases (TrXs). We propose in this study that the overproduction of Sec via the overexpression of Selenocysteine synthase (SecS) gene and Se supplementation induced cell death in Prostate Carcinoma (PC-3) cells. Although the mechanism underlying the cell death induction is unknown, we propose it could be due to the random incorporation of Sec into proteins at high concentration, causing premature protein degradation and cell death. The outcome of this study showed that increasing the concentration of intracellular Se-containing amino acids may provide important clinical implications for the treatment of cancer.
文摘Selenocysteine, a selenium-containing analog of cysteine, is found in the prokaryotic and eukaryotic kingdoms in active sites of enzymes involved in oxidation-reduction reactions. This aminoacid is cotranslationally incorporated at UGA codons which usually act as translation stop codons. In eukaryotes, decoding of selenocysteine necessitates the participation of the selenocysteine insertion sequence (SECIS), an element lying in the 3' -untranslated region of selenoprotein mRNAs. A detailed experimental study of the secondary structures of the SECIS elements of rat and human type 1 iodothyronine deiodinases and rat glutathione peroxidase was performed. Enzymatic and chemical structure probing led us to propose a secondary structure model, supported by sequence comparison of 23 SECIS mRNAs. The secondary structure model revealed the existence of a novel type of RNA motif composed of four consecutive non-Watson-Crick base-pairs. Using gel shift experiments, we identified in several mammalian cell type extracts the protein SBP,for SECIS-binding protein, that specifically recognizes the iodothyronine deiodinases and glutathione peroxidase SECIS elements. The structural model that we derived for the SECIS RNAs discloses RNA features possibly implicated in the binding of SBP and/or SECIS function
基金the Projects of International Cooperation National Key R&D Program of China(Grant No.2022YFE0108300)the National Key Research and Development Program of China(Grant No.2022YFF1003000)the National Natural Science Foundation of China(Grant Nos.32372682,32272747,32072585,32072568).
文摘Selenocysteine methyltransferase(SMT)is a key enzyme involved in the Se metabolism pathway,and it is responsible for the catalysis of Se-methylselenocysteine(SeMSC)compound formation.Previous studies showed that selenium treatment activated SMT expression and promoted the accumulation of glucosinolates(GSLs)and sulforaphane,but the roles and functional mechanisms of SMT in mediating GSLs and sulforaphane synthesis remain unclear.In this study,we identified the BoSMT gene in broccoli and uncovered its roles in mediating GSLs biosynthesis.Transgenic assays revealed that BoSMT is involved in SeMSC biosynthesis in broccoli.More importantly,the contents of GSLs and sulforaphane were significantly increased in the BoSMT-overexpressing broccoli lines but decreased in the knockdown lines,suggesting that BoSMT played a positive role in regulating GSLs and sulforaphane synthesis.Further evidence indicated that BoSMT-mediated overaccumulation of GSLs and sulforaphane might be due to the increase in the endogenous SeMSC content.Compared with the mock(water)treatment,selenite-induced significantly increases of the SeMSC content in the BoSMT-knockdown plants partially compensated the phenotype of GSLs and sulforaphane loss.Compared with the mock treatment,exogenous SeMSC treatment significantly increased the contents of GSL and sulforaphane and activated GSL synthesis-related gene expression,suggesting that SeMSC acted as a positive regulator for GSL and sulforaphane production.Our findings provided novel insights into selenium-mediated GSLs and sulforaphane accumulation.The genetic manipulation of BoSMT might be a useful strategy for improving the dietary nutritional values of broccoli.
基金supported by the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(32171970)the Chongqing Outstanding Scientists Project(cstc2022ycjh-bgzxm0073)the Natural Science Foundation of Chongqing,China(cstc2021jcyj-cxttX0004)。
文摘Anther dehiscence controls optimal interaction between pollen and stigma,thereby determining the successful sexual reproduction.The regulators or mechanisms of this process remain elusive.Here,two CRISPR/Cas9 mutants of a rice exocyst subunit gene SEC3A,sec3a-1 and sec3a-2,showed anther indehiscence at anthesis and male sterility at maturity.Pollen viability and germination in the mutants were partly defective,whereas their female gametes undergone a normal development.Hybrid or self-pollinated seeds could be produced by artificial pollination,suggesting potential use of a weak sec3a mutant as a female line during hybrid breeding.SEC3A is widely expressed in various tissues,including anther walls.Further results showed an excessive IAA accumulation and no endothecium lignification in sec3a-1/2 anthers.Our findings suggest that SEC3A appears to regulate anther dehiscence by modulating auxin signaling,providing insights into regulation of anther dehiscence and function of exocyst in plants.