Riboswitches are highly conserved RNA elements that located in the 5’-UTR of m RNAs,which undergo real-time structure conformational change to achieve the regulation of downstream gene expression by sensing their cog...Riboswitches are highly conserved RNA elements that located in the 5’-UTR of m RNAs,which undergo real-time structure conformational change to achieve the regulation of downstream gene expression by sensing their cognate ligands.S-adenosylmethionine(SAM)is a ubiquitous methyl donor for transmethylation reactions in all living organisms.SAM riboswitch is one of the most abundant riboswitches that bind to SAM with high affinity and selectivity,serving as regulatory modules in multiple metabolic pathways.To date,seven SAM-specific riboswitch classes that belong to four families,one SAM/SAH riboswitch and one SAH riboswitch have been identified.Each SAM riboswitch family has a well-organized tertiary core scaffold to support their unique ligand-specific binding pocket.In this review,we summarize the current research progress on the distribution,structure,ligand recognition and gene regulation mechanism of these SAM-related riboswitch families,and further discuss their evolutionary prospects and potential applications.展开更多
OBJECTIVE:To investigate the relationship between antiviral restriction factor Sterile Alpha Motif and Histidine-Aspartic acid domain-containing protein 1(SAMHD1)expression and T cell activation,furthermore,identifyin...OBJECTIVE:To investigate the relationship between antiviral restriction factor Sterile Alpha Motif and Histidine-Aspartic acid domain-containing protein 1(SAMHD1)expression and T cell activation,furthermore,identifying objective indexes of lung-spleen Qi deficiency symptom pattern.METHODS:We assessed the profile of T lymphocyte subsets,characteristics of SAMHD1 and human leukocyte antigen DR(HLA-DR)expression in lungspleen Qi deficiency patients.At the same time,people living with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS)(PLWHA)without obvious clinical symptoms and healthy donors in this area were used as controls.RESULTS:Immunohematologic indexes lower CD4 count,lower CD4/CD8 ratio and higher SAMHD1 level were found in lung-spleen Qi deficiency patients.Furthermore,we demonstrated a positive relationship between SAMHD1 and HLA-DR level as well as with interferon factor in lung-spleen Qi deficiency syndrome and patients without obvious clinical signs and symptoms groups.CONCLUSIONS:These data indicated the positive relationship between SAMHD1 and T cell activation which further elucidated the role of SAMHD1 in cellular immune response.Furthermore,combination of T lymphocyte subsets counts and SAMHD1 level may be used as clinical and biological reference basis for the differentiation and diagnosis of HIV/AIDS traditional Chinese medicine syndromes.展开更多
Cell migration is a finely tuned biological process that often involves epithelial-mesenchymal transition(EMT).EMT is typically characterized by the upregulation of mesenchymal markers such as Snail1.This process has ...Cell migration is a finely tuned biological process that often involves epithelial-mesenchymal transition(EMT).EMT is typically characterized by the upregulation of mesenchymal markers such as Snail1.This process has been shown to be of critical importance to normal developmental processes,including neural crest migration and invasion.Interestingly,similar mechanisms are utilized in disease processes,such as tumor metastasis and migration.Notably,EMT and EMT-like processes confer tumor cells with the ability to migrate,invade,and adopt stem cell-like properties that largely account for immunosuppression and tumor recurrence.Therefore,identifying sensitive EMT markers may contribute to cancer prognosis and diagnosis in many facets.Previously,we showed that Elp3 plays an essential role during neural crest migration by stabilizing Snail1.In the current study,we further elucidate the molecular mechanism underlying colorectal cancer migration.We found that mElp3 exerted an identical function to xElp3 in modulating neural crest migration,and both HAT and SAM domains are imperative during this migratory process.Interestingly,overexpression of mElp3 in SW480 cells promoted cell migration and invasion,and we further showed that Elp3 stabilized Snail1 requiring integrity of both SAM and HAT domains.Our findings warrant further exploration of the specific target of Elp3 in cancer cells.展开更多
基金supported by the National Natural Science Foundation of China(32022039,31870810,91940302,91640104)the National Key Research and Development Project of China(2021YFC2300300)+2 种基金the China Postdoctoral Science Foundation(2022M713637)the Outstanding Youth Fund of Zhejiang Province(LR19C050003)the Fundamental Research Funds for the Central Universities(2017QN81010)。
文摘Riboswitches are highly conserved RNA elements that located in the 5’-UTR of m RNAs,which undergo real-time structure conformational change to achieve the regulation of downstream gene expression by sensing their cognate ligands.S-adenosylmethionine(SAM)is a ubiquitous methyl donor for transmethylation reactions in all living organisms.SAM riboswitch is one of the most abundant riboswitches that bind to SAM with high affinity and selectivity,serving as regulatory modules in multiple metabolic pathways.To date,seven SAM-specific riboswitch classes that belong to four families,one SAM/SAH riboswitch and one SAH riboswitch have been identified.Each SAM riboswitch family has a well-organized tertiary core scaffold to support their unique ligand-specific binding pocket.In this review,we summarize the current research progress on the distribution,structure,ligand recognition and gene regulation mechanism of these SAM-related riboswitch families,and further discuss their evolutionary prospects and potential applications.
基金Supported by the National Natural Science Foundation of China(Construction of HIV Pseudovirus Infected Cell Model and Application of Yiaikang in the Study of T Cell Immune Response,No.82004207)the National Special Science and Technology Program on Major Infectious Diseases(Study on the Scheme of TCM to Reduce the Incidence of Adverse Reactions to AIDS Antiviral Therapy,No.2017ZX10205502002+6 种基金Study on the Scheme of TCM to Reduce the Incidence of AIDS Opportunistic Infection,No.2017ZX10205502003)the Science and Technology Tackling Plan of Henan Province(Exploring the Activation Mechanism of Yiaikang on CD8+T Lymphocytes in HIV/AIDS Patients based on STING/SAMHD1 Pathway,No.202102310178Regulation of HIV/AIDS Treg CellDerived Exosomeso on Activation of CD4+T Cells and the Intervention of Yiaikang,No.212102311126)Subject Construction Project of Henan Characteristic Backbone Subject of TCM of Henan University of TCM(Deep Sequencing/Molecular Docking/Gene Editing Network System to Analyze The Mechanism of TCM Regulating the Immune Function of HIV Patients,No.STG-ZYXKY-2020029)Henan Province TCM Research Project(Explore the Mechanism of Yiaikang in the Treatment of AIDS Immunity Based on HIV gag-CTL Response,No.2018JDZX106,2019AZB003Study on TCM Treatment of Aged AIDS,No.20-21ZYZD03)Key Scientific Research Projects of Colleges and Universities in Henan Province(to Explore the Regulation Mechanism of Yiaikang on AIDS Lung Qi Deficiency Syndrome from TGF-β/Smad/ID,No.20A360010)
文摘OBJECTIVE:To investigate the relationship between antiviral restriction factor Sterile Alpha Motif and Histidine-Aspartic acid domain-containing protein 1(SAMHD1)expression and T cell activation,furthermore,identifying objective indexes of lung-spleen Qi deficiency symptom pattern.METHODS:We assessed the profile of T lymphocyte subsets,characteristics of SAMHD1 and human leukocyte antigen DR(HLA-DR)expression in lungspleen Qi deficiency patients.At the same time,people living with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS)(PLWHA)without obvious clinical symptoms and healthy donors in this area were used as controls.RESULTS:Immunohematologic indexes lower CD4 count,lower CD4/CD8 ratio and higher SAMHD1 level were found in lung-spleen Qi deficiency patients.Furthermore,we demonstrated a positive relationship between SAMHD1 and HLA-DR level as well as with interferon factor in lung-spleen Qi deficiency syndrome and patients without obvious clinical signs and symptoms groups.CONCLUSIONS:These data indicated the positive relationship between SAMHD1 and T cell activation which further elucidated the role of SAMHD1 in cellular immune response.Furthermore,combination of T lymphocyte subsets counts and SAMHD1 level may be used as clinical and biological reference basis for the differentiation and diagnosis of HIV/AIDS traditional Chinese medicine syndromes.
基金supported by the National Natural Science Foundation of China(Grant Nos.81760503 and 81760660)the Applied Basic Research Key Project of Yunnan(Grant Nos.2018FE001(-318)and 2018FE001(-123))the Yunnan Health Science and Technology Plan Projects(Grant No.2016NS207).
文摘Cell migration is a finely tuned biological process that often involves epithelial-mesenchymal transition(EMT).EMT is typically characterized by the upregulation of mesenchymal markers such as Snail1.This process has been shown to be of critical importance to normal developmental processes,including neural crest migration and invasion.Interestingly,similar mechanisms are utilized in disease processes,such as tumor metastasis and migration.Notably,EMT and EMT-like processes confer tumor cells with the ability to migrate,invade,and adopt stem cell-like properties that largely account for immunosuppression and tumor recurrence.Therefore,identifying sensitive EMT markers may contribute to cancer prognosis and diagnosis in many facets.Previously,we showed that Elp3 plays an essential role during neural crest migration by stabilizing Snail1.In the current study,we further elucidate the molecular mechanism underlying colorectal cancer migration.We found that mElp3 exerted an identical function to xElp3 in modulating neural crest migration,and both HAT and SAM domains are imperative during this migratory process.Interestingly,overexpression of mElp3 in SW480 cells promoted cell migration and invasion,and we further showed that Elp3 stabilized Snail1 requiring integrity of both SAM and HAT domains.Our findings warrant further exploration of the specific target of Elp3 in cancer cells.