Immersed tunnel is an important part of the Hong Kong–Zhuhai–Macao Bridge(HZMB) project. In immersed tunnel floating, translation which includes straight and transverse movements is the main working mode. To decide ...Immersed tunnel is an important part of the Hong Kong–Zhuhai–Macao Bridge(HZMB) project. In immersed tunnel floating, translation which includes straight and transverse movements is the main working mode. To decide the magnitude and direction of the towing force for each tug, a particle swarm-based translation control method is presented for non-power immersed tunnel element. A sort of linear weighted logarithmic function is exploited to avoid weak subgoals. In simulation, the particle swarm-based control method is evaluated and compared with traditional empirical method in the case of the HZMB project. Simulation results show that the presented method delivers performance improvement in terms of the enhanced surplus towing force.展开更多
Messenger RNA(mRNA)translation consists of initiation,elongation,termination,and ribosome recycling,carried out by the translation machinery,primarily including tRNAs,ribosomes,and translation factors(TrFs).Translatio...Messenger RNA(mRNA)translation consists of initiation,elongation,termination,and ribosome recycling,carried out by the translation machinery,primarily including tRNAs,ribosomes,and translation factors(TrFs).Translational regulators transduce signals of growth and development,as well as biotic and abiotic stresses,to the translation machinery,where global or selective translational control occurs to modulate mRNA translation efficiency(TrE).As the basis of translational control,the translation machinery directly determines the quality and quantity of newly synthesized peptides and,ultimately,the cellular adaption.Thus,regulating the availability of diverse machinery components is reviewed as the central strategy of translational control.We provide classical signaling pathways(e.g.,integrated stress responses)and cellular behaviors(e.g.,liquideliquid phase separation)to exemplify this strategy within different physiological contexts,particularly during hostemicrobe interactions.With new technologies developed,further understanding this strategy will speed up translational medicine and translational agriculture.展开更多
A homologue of the lower vertebrates translationally controlled tumor protein (TCTP) was cloned from the marine fish Japanese sea perch (Lateolabrax japonicus) by the technology of homology cloning. The full-length cD...A homologue of the lower vertebrates translationally controlled tumor protein (TCTP) was cloned from the marine fish Japanese sea perch (Lateolabrax japonicus) by the technology of homology cloning. The full-length cDNA sequence of the sea perch TCTP gene contained a 5' untranslated region (UTR) of 47 bp, a 3' UTR of 433 bp, and a putative open reading frame (ORF) of 510 bp encoding a polypeptide of 170 amino acids. The deduced amino acid sequence of the sea perch TCTP gene showed a high similarity to that of zebrafish, rohu, rabbit, chicken and human. Sequence analysis revealed there were a signature sequence of TCTP family, an N-glycosylation site, and five Casein kinase phosphorylation sites in the sea perch TCTP. The temporal expression of TCTP genes in healthy and lipopolysaccharide (LPS) challenged fishes was measured by semi-quantitative reverse transcription-PCR (RT-PCR). The results indicated that LPS could up-regulate the expression of sea perch TCTP in the examined tissues, including head-kidney, spleen and liver.展开更多
The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbe...The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.展开更多
A full-length cDNA encoding translationally controlled tumor protein of marine flatfish turbot （Scophthalmus maximus）, SmTCTP, was isolated with rapid amplification of cDNA Ends （RACE）. SmTCTP consisted of a 5＇ u...A full-length cDNA encoding translationally controlled tumor protein of marine flatfish turbot （Scophthalmus maximus）, SmTCTP, was isolated with rapid amplification of cDNA Ends （RACE）. SmTCTP consisted of a 5＇ untranslated region （UTR） of 84 bp, a 3＇ UTR of 451 bp and an open reading frame （ORF） of 513 bp, encoding a protein of 170 amino acid residues, which contained two signature sequences of TCTP family. The 5＇UTR of SmTCTP started with a 5＇-terminal oligopyrimidine tract （5＇-TOP）, a typical feature for translationally controlled mRNAs. The deduced amino acid sequence of SmTCTP was similar to the other known vertebrate TCTPs in a range of 58.8% to 64.1%. The length of fish TCTPs was diverse among species, e.g., TCTP of turbot and sea perch （Lateolabraxjaponicus） is 170 aa in length, while that of zebrafish （Danio rerio） and rohu （Labeo rohita） is 171 aa in length. Northern blot analysis revealed that SmTCTP has only one type of mRNA. Its expression level in albino skin was slightly higher than that in normal skin. We constructed the pET3Oa-SmTCTP expression plasmid. The recombinant protein of His-tag SmTCTP was over-expressed in E. coli, purified and identified with peptide mass fingerprinting. These results may pave the way of further investigation of the biological function of TCTP in fish.展开更多
Translationally controlled tumor protein(TCTP) is a highly conserved multifunctional protein localized in the cytoplasm and nucleus of eukaryotic cells. It is secreted through exosomes and its degradation is associate...Translationally controlled tumor protein(TCTP) is a highly conserved multifunctional protein localized in the cytoplasm and nucleus of eukaryotic cells. It is secreted through exosomes and its degradation is associated with the ubiquitin-proteasome system(UPS), heat shock protein 27(Hsp27), and chaperone-mediated autophagy(CMA). Its structure contains three α-helices and eleven β-strands, and features a helical hairpin as its hallmark. TCTP shows a remarkable similarity to the methionine-R-sulfoxide reductase B(Msr B) and mammalian suppressor of Sec4(Mss4/Dss4) protein families, which exerts guanine nucleotide exchange factor(GEF) activity on small guanosine triphosphatase(GTPase) proteins, suggesting that some functions of TCTP may at least depend on its GEF action. Indeed, TCTP exerts GEF activity on Ras homolog enriched in brain(Rheb) to boost the growth and proliferation of Drosophila cells. TCTP also enhances the expression of cell division control protein 42 homolog(Cdc42) to promote cancer cell invasion and migration. Moreover, TCTP regulates cytoskeleton organization by interacting with actin microfilament(MF) and microtubule(MT) proteins and inducing the epithelial-mesenchymal transition(EMT) process. In essence, TCTP promotes cancer cell movement. It is usually highly expressed in cancerous tissues and thus reduces patient survival;meanwhile, drugs can target TCTP to reduce this effect. In this review, we summarize the mechanisms of TCTP in promoting cancer invasion and migration, and describe the current inhibitory strategy to target TCTP in cancerous diseases.展开更多
Autophagy is an evolutionarily conserved lysosome-mediated catabolic process（Klionsky,2007）.Autophagy is believed to be essential for cell survival,especially when cells were exposed to stresses,such as nutrient sta...Autophagy is an evolutionarily conserved lysosome-mediated catabolic process（Klionsky,2007）.Autophagy is believed to be essential for cell survival,especially when cells were exposed to stresses,such as nutrient starvation.展开更多
Background:Translationally controlled tumor protein(TCTP),which has been verified to have a proinflammatory activity,plays an important role in allergy.However,it remains unclear whether TCTP has an impact on the acut...Background:Translationally controlled tumor protein(TCTP),which has been verified to have a proinflammatory activity,plays an important role in allergy.However,it remains unclear whether TCTP has an impact on the acute rejection(AR)after liver transplantation.Methods:Three protocols were used to delineate the role of TCTP in AR after liver transplantation.First,in rat orthotopic liver transplantation(OLT),the expression of TCTP was measured by enzyme-linked immunosorbent assay(ELISA),real-time PCR,Western blot and immunofluorescence assays.Second,in mixed lymphocyte reaction(MLR),the role of TCTP in lymphocyte proliferation was measured by carboxyfluorescein succinimidyl ester(CFSE)labeling and the impact of TCTP on inflammatory factor release was detected by cytokine arrays.Third,in human OLT,the level of serum TCTP was detected by ELISA,and the relationship between TCTP and model for early allograft function(MEAF)score was assessed by Spearman's correlation.Results:In rat OLT,AR resulted in great harm to allografts,manifesting as deterioration of liver function,increasing inflammatory factors and infiltrating lymphocytes.Meanwhile,TCTP was overexpressed in serum and allografts.Higher level of TCTP was associated with higher rejection activity index(RAI).In an MLR protocol,TCTP knockdown inhibited the proliferation of mixed inflammatory cells and significantly suppressed the release of 15 cytokines and chemokines.In human OLT,the serum TCTP was up-regulated within a week after operation.Additionally,the increasing speed of serum TCTP positively correlated with MEAF scores(r=0.449;P=0.0088).展开更多
This paper addresses an integrated relative position and attitude control strategy for a pursuer spacecraft flying to a space target in proximity operation missions. Relative translation and rotation dynamics are both...This paper addresses an integrated relative position and attitude control strategy for a pursuer spacecraft flying to a space target in proximity operation missions. Relative translation and rotation dynamics are both presented, and further integratedly considered due to mutual couplings, which results in a six degrees-of-freedom (6-DOF) control system. In order to simultaneously achieve relative position and attitude requirements, an adaptive backstepping control law is designed, where a command filter is introduced to overcome 'explosion of terms'. Within the Lyapunov framework, the proposed controller is proved to ensure the ultimate boundedness of relative position and attitude signals, in the presence of external disturbances and unknown system parameters. Numerical simulation demonstrates the effect of the designed control law.展开更多
PKR, the interferon （IFN）-inducible protein kinase activated by double-stranded RNA, inhibits translation by phosphorylating the initiation factor eIF2α chain. Uniquely, human IFN-γ mRNA uses local activation of P...PKR, the interferon （IFN）-inducible protein kinase activated by double-stranded RNA, inhibits translation by phosphorylating the initiation factor eIF2α chain. Uniquely, human IFN-γ mRNA uses local activation of PKR in the cell to control its own translation yield. IFN-γ mRNA activates PKR through a structure in its 5＇- region harboring a pseudoknot which is critical for PKR activation. Mutations that impair pseudoknot stability reduce the ability of IFN-γ mRNA to activate PKR and strongly increase its translation efficiency. The cis-acting RNA element in IFN-γ mRNA functions as a biological sensor of intracellular PKR levels. During an immune response, as IFN-γ and other inflammatory cytokines build up in the cell＇s microenvironment, they act to induce higher levels of PKR in the cell, resulting in a more extensive activation of PKR by IFN-γ mRNA. With the resulting phosphorylation of eIF2α, a negative feedback loop is created and the production of IFN-γ is progressively attenuated. We propose that the therapeutic effect of IFN-β in multiple sclerosis may rest, at least in part, on its exquisite ability to induce high levels of PKR in the cell and thereby to limit IFN-γ mRNA translation through this negative feedback loop, blocking the excessive IFN-γ gene expression that precedes clinical attacks.展开更多
The expression of a gene is governed at various levels,from transcriptional to translational level.The translational control is widely used to regulate gene expression,especially when a rapid,local,and selective contr...The expression of a gene is governed at various levels,from transcriptional to translational level.The translational control is widely used to regulate gene expression,especially when a rapid,local,and selective control over protein synthesis is required.The present review describes instructive examples of translational regulation in yeast,together with regulatory elements within mRNAs.The review also outlines the important contributions of mRNA-binding proteins that act in harmony with several translational elements to generate appropriate translational signals and responses.展开更多
A 5'-leader,known initially as the 5'-untranslated region,contains multiple isoforms due to alternative splicing(aS)and alternative transcription start site(aTSS).Therefore,a representative 5'-leader is de...A 5'-leader,known initially as the 5'-untranslated region,contains multiple isoforms due to alternative splicing(aS)and alternative transcription start site(aTSS).Therefore,a representative 5'-leader is demanded to examine the embedded RNA regulatory elements in controlling translation efficiency.Here,we develop a ranking algorithm and a deep-learning model to annotate representative 5'-leaders for five plant species.We rank the intra-sample and inter-sample frequency of aS-mediated transcript isoforms using the Kruskal-Wallis test-based algorithm and identify the representative aS-5'-leader.To further assign a representative 5'-end,we train the deep-learning model 5'leaderP to learn aTsS-mediated 5'-end distribution patterns from cap-analysis gene expression data.The model accurately predicts the 5'-end,confirmed experimentally in Arabidopsis and rice.The representative 5'-leader-contained gene models and 5'leaderP can be accessed at RNAirport(http:/www.rnairport.com/leader5P/).The Stage 1 annotation of 5'-leader records 5'-leader diversity and will pave the way to Ribo-Seq open-reading frame annotation,identical to the project recently initiated by human GENCODE.展开更多
基金financially supported by the Ministry of Education of Humanities and Social Science Project(Grant Nos.15YJC630145 and 15YJC630059)the Natural Science Foundation of Shanghai Science and Technology Committee(Grant No.15ZR1420200)
文摘Immersed tunnel is an important part of the Hong Kong–Zhuhai–Macao Bridge(HZMB) project. In immersed tunnel floating, translation which includes straight and transverse movements is the main working mode. To decide the magnitude and direction of the towing force for each tug, a particle swarm-based translation control method is presented for non-power immersed tunnel element. A sort of linear weighted logarithmic function is exploited to avoid weak subgoals. In simulation, the particle swarm-based control method is evaluated and compared with traditional empirical method in the case of the HZMB project. Simulation results show that the presented method delivers performance improvement in terms of the enhanced surplus towing force.
基金supported by grants from the National Natural Science Foundation of China(32070284)the Major Project of Hubei Hongshan Laboratory(2022hszd016)the Key Research and Development Program of Hubei Province(2022BFE003)to G.Xu.We apologize to colleagues whose excellent work was not cited in this review due to the space limit.
文摘Messenger RNA(mRNA)translation consists of initiation,elongation,termination,and ribosome recycling,carried out by the translation machinery,primarily including tRNAs,ribosomes,and translation factors(TrFs).Translational regulators transduce signals of growth and development,as well as biotic and abiotic stresses,to the translation machinery,where global or selective translational control occurs to modulate mRNA translation efficiency(TrE).As the basis of translational control,the translation machinery directly determines the quality and quantity of newly synthesized peptides and,ultimately,the cellular adaption.Thus,regulating the availability of diverse machinery components is reviewed as the central strategy of translational control.We provide classical signaling pathways(e.g.,integrated stress responses)and cellular behaviors(e.g.,liquideliquid phase separation)to exemplify this strategy within different physiological contexts,particularly during hostemicrobe interactions.With new technologies developed,further understanding this strategy will speed up translational medicine and translational agriculture.
基金supported by the“863"Prijetof China under contract Nos 2001AA628180 and 2002AA626020.
文摘A homologue of the lower vertebrates translationally controlled tumor protein (TCTP) was cloned from the marine fish Japanese sea perch (Lateolabrax japonicus) by the technology of homology cloning. The full-length cDNA sequence of the sea perch TCTP gene contained a 5' untranslated region (UTR) of 47 bp, a 3' UTR of 433 bp, and a putative open reading frame (ORF) of 510 bp encoding a polypeptide of 170 amino acids. The deduced amino acid sequence of the sea perch TCTP gene showed a high similarity to that of zebrafish, rohu, rabbit, chicken and human. Sequence analysis revealed there were a signature sequence of TCTP family, an N-glycosylation site, and five Casein kinase phosphorylation sites in the sea perch TCTP. The temporal expression of TCTP genes in healthy and lipopolysaccharide (LPS) challenged fishes was measured by semi-quantitative reverse transcription-PCR (RT-PCR). The results indicated that LPS could up-regulate the expression of sea perch TCTP in the examined tissues, including head-kidney, spleen and liver.
文摘The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.
文摘A full-length cDNA encoding translationally controlled tumor protein of marine flatfish turbot （Scophthalmus maximus）, SmTCTP, was isolated with rapid amplification of cDNA Ends （RACE）. SmTCTP consisted of a 5＇ untranslated region （UTR） of 84 bp, a 3＇ UTR of 451 bp and an open reading frame （ORF） of 513 bp, encoding a protein of 170 amino acid residues, which contained two signature sequences of TCTP family. The 5＇UTR of SmTCTP started with a 5＇-terminal oligopyrimidine tract （5＇-TOP）, a typical feature for translationally controlled mRNAs. The deduced amino acid sequence of SmTCTP was similar to the other known vertebrate TCTPs in a range of 58.8% to 64.1%. The length of fish TCTPs was diverse among species, e.g., TCTP of turbot and sea perch （Lateolabraxjaponicus） is 170 aa in length, while that of zebrafish （Danio rerio） and rohu （Labeo rohita） is 171 aa in length. Northern blot analysis revealed that SmTCTP has only one type of mRNA. Its expression level in albino skin was slightly higher than that in normal skin. We constructed the pET3Oa-SmTCTP expression plasmid. The recombinant protein of His-tag SmTCTP was over-expressed in E. coli, purified and identified with peptide mass fingerprinting. These results may pave the way of further investigation of the biological function of TCTP in fish.
基金funded by the National Natural Science Foundation of China(No.31672377)。
文摘Translationally controlled tumor protein(TCTP) is a highly conserved multifunctional protein localized in the cytoplasm and nucleus of eukaryotic cells. It is secreted through exosomes and its degradation is associated with the ubiquitin-proteasome system(UPS), heat shock protein 27(Hsp27), and chaperone-mediated autophagy(CMA). Its structure contains three α-helices and eleven β-strands, and features a helical hairpin as its hallmark. TCTP shows a remarkable similarity to the methionine-R-sulfoxide reductase B(Msr B) and mammalian suppressor of Sec4(Mss4/Dss4) protein families, which exerts guanine nucleotide exchange factor(GEF) activity on small guanosine triphosphatase(GTPase) proteins, suggesting that some functions of TCTP may at least depend on its GEF action. Indeed, TCTP exerts GEF activity on Ras homolog enriched in brain(Rheb) to boost the growth and proliferation of Drosophila cells. TCTP also enhances the expression of cell division control protein 42 homolog(Cdc42) to promote cancer cell invasion and migration. Moreover, TCTP regulates cytoskeleton organization by interacting with actin microfilament(MF) and microtubule(MT) proteins and inducing the epithelial-mesenchymal transition(EMT) process. In essence, TCTP promotes cancer cell movement. It is usually highly expressed in cancerous tissues and thus reduces patient survival;meanwhile, drugs can target TCTP to reduce this effect. In this review, we summarize the mechanisms of TCTP in promoting cancer invasion and migration, and describe the current inhibitory strategy to target TCTP in cancerous diseases.
基金supported by the National Basic Research Program of China (973 Program)(No.2016YFA0100400)the National Natural Science Foundation of China(No.81773009)
文摘Autophagy is an evolutionarily conserved lysosome-mediated catabolic process（Klionsky,2007）.Autophagy is believed to be essential for cell survival,especially when cells were exposed to stresses,such as nutrient starvation.
基金supported by grants from the National Key Research and Development Program Funded Projects(2017YFC1103703)National Basic Research Program of China(2015CB554100)National Natural Science Foundation(81870446,81670593and 81900571)。
文摘Background:Translationally controlled tumor protein(TCTP),which has been verified to have a proinflammatory activity,plays an important role in allergy.However,it remains unclear whether TCTP has an impact on the acute rejection(AR)after liver transplantation.Methods:Three protocols were used to delineate the role of TCTP in AR after liver transplantation.First,in rat orthotopic liver transplantation(OLT),the expression of TCTP was measured by enzyme-linked immunosorbent assay(ELISA),real-time PCR,Western blot and immunofluorescence assays.Second,in mixed lymphocyte reaction(MLR),the role of TCTP in lymphocyte proliferation was measured by carboxyfluorescein succinimidyl ester(CFSE)labeling and the impact of TCTP on inflammatory factor release was detected by cytokine arrays.Third,in human OLT,the level of serum TCTP was detected by ELISA,and the relationship between TCTP and model for early allograft function(MEAF)score was assessed by Spearman's correlation.Results:In rat OLT,AR resulted in great harm to allografts,manifesting as deterioration of liver function,increasing inflammatory factors and infiltrating lymphocytes.Meanwhile,TCTP was overexpressed in serum and allografts.Higher level of TCTP was associated with higher rejection activity index(RAI).In an MLR protocol,TCTP knockdown inhibited the proliferation of mixed inflammatory cells and significantly suppressed the release of 15 cytokines and chemokines.In human OLT,the serum TCTP was up-regulated within a week after operation.Additionally,the increasing speed of serum TCTP positively correlated with MEAF scores(r=0.449;P=0.0088).
基金supported by Innovative Team Program of the National Natural Science Foundation of China (No.61021002)
文摘This paper addresses an integrated relative position and attitude control strategy for a pursuer spacecraft flying to a space target in proximity operation missions. Relative translation and rotation dynamics are both presented, and further integratedly considered due to mutual couplings, which results in a six degrees-of-freedom (6-DOF) control system. In order to simultaneously achieve relative position and attitude requirements, an adaptive backstepping control law is designed, where a command filter is introduced to overcome 'explosion of terms'. Within the Lyapunov framework, the proposed controller is proved to ensure the ultimate boundedness of relative position and attitude signals, in the presence of external disturbances and unknown system parameters. Numerical simulation demonstrates the effect of the designed control law.
基金Acknowledgements Research in the author＇s laboratory was supported by grants from the Israel Science Foundation （537/03） and the Deutsche Forschungsgemeinschaft （H0- 1116）,
文摘PKR, the interferon （IFN）-inducible protein kinase activated by double-stranded RNA, inhibits translation by phosphorylating the initiation factor eIF2α chain. Uniquely, human IFN-γ mRNA uses local activation of PKR in the cell to control its own translation yield. IFN-γ mRNA activates PKR through a structure in its 5＇- region harboring a pseudoknot which is critical for PKR activation. Mutations that impair pseudoknot stability reduce the ability of IFN-γ mRNA to activate PKR and strongly increase its translation efficiency. The cis-acting RNA element in IFN-γ mRNA functions as a biological sensor of intracellular PKR levels. During an immune response, as IFN-γ and other inflammatory cytokines build up in the cell＇s microenvironment, they act to induce higher levels of PKR in the cell, resulting in a more extensive activation of PKR by IFN-γ mRNA. With the resulting phosphorylation of eIF2α, a negative feedback loop is created and the production of IFN-γ is progressively attenuated. We propose that the therapeutic effect of IFN-β in multiple sclerosis may rest, at least in part, on its exquisite ability to induce high levels of PKR in the cell and thereby to limit IFN-γ mRNA translation through this negative feedback loop, blocking the excessive IFN-γ gene expression that precedes clinical attacks.
文摘The expression of a gene is governed at various levels,from transcriptional to translational level.The translational control is widely used to regulate gene expression,especially when a rapid,local,and selective control over protein synthesis is required.The present review describes instructive examples of translational regulation in yeast,together with regulatory elements within mRNAs.The review also outlines the important contributions of mRNA-binding proteins that act in harmony with several translational elements to generate appropriate translational signals and responses.
基金supported by grants from the National Key R&D Program of China(2023ZD04073)the Major Project of Hubei Hongshan Laboratory(2022hszd016)+1 种基金the Key Research and Development Program of Hubei Province(2022BFE003)the National Natural Science Foundation of China(32070284)to G.Xu.
文摘A 5'-leader,known initially as the 5'-untranslated region,contains multiple isoforms due to alternative splicing(aS)and alternative transcription start site(aTSS).Therefore,a representative 5'-leader is demanded to examine the embedded RNA regulatory elements in controlling translation efficiency.Here,we develop a ranking algorithm and a deep-learning model to annotate representative 5'-leaders for five plant species.We rank the intra-sample and inter-sample frequency of aS-mediated transcript isoforms using the Kruskal-Wallis test-based algorithm and identify the representative aS-5'-leader.To further assign a representative 5'-end,we train the deep-learning model 5'leaderP to learn aTsS-mediated 5'-end distribution patterns from cap-analysis gene expression data.The model accurately predicts the 5'-end,confirmed experimentally in Arabidopsis and rice.The representative 5'-leader-contained gene models and 5'leaderP can be accessed at RNAirport(http:/www.rnairport.com/leader5P/).The Stage 1 annotation of 5'-leader records 5'-leader diversity and will pave the way to Ribo-Seq open-reading frame annotation,identical to the project recently initiated by human GENCODE.
