BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the gene...BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the genetic basis remains unclear for several patients.AIM To investigate the involvement of UBE3A gene in AS and identifying new potential genes using exome sequencing.METHODS We established a cohort study in 50 patients referred to Farhat Hached University Hospital between 2006 and 2021,with a strong suspicion of AS and absence of chromosomal aberrations.The UBE3A gene was screened for mutation detection.Two unrelated patients issued from consanguineous families were subjected to exome analysis.RESULTS We describe seven UBE3A variants among them 3 none previously described including intronic variants c.2220+14T>C(intron14),c.2507+43T>A(Exon15)and insertion in Exon7:c.30-47_30-46.The exome sequencing revealed 22 potential genes that could be involved in AS-like syndromes that should be investigated further.CONCLUSION Screening for UBE3A mutations in AS patients has been proven to be useful to confirm the diagnosis.Our exome findings could rise to new potential alternative target genes for genetic counseling.展开更多
Macrophages,existed in almost all organs of the body,are responsible for detecting tissue injury,pathogens,playing a key role in host defense against a variety of invading pathogens triggering inflammatory responses.E...Macrophages,existed in almost all organs of the body,are responsible for detecting tissue injury,pathogens,playing a key role in host defense against a variety of invading pathogens triggering inflammatory responses.Emerging evidence suggests that macrophage-mediated immune responses are efficiently regulated by the ubiquitination modification,which is responsible for normal immune responses.However,numerous studies indicates that the aberrant activation or inhibition of macrophage-mediated immune responses occurs in inflammation,mainly caused by dysregulated ubiquitination modification due to E3 ubiquitin ligases mutations or abnormal expression.Notably,E3 ubiquitin ligases,responsible for recognizing the substrates,are key enzymes in the ubiquitin proteasome system(UPS)composed of ubiquitin(Ub),ubiquitin-activating E1 enzymes,ubiquitin-conjugating E2 enzymes,E3 ubiquitin ligases,26S proteasome,and deubiquitinating enzymes.Intriguingly,several E3 ubiquitin ligases are involved in the regulation of some common signal pathways in macrophage-mediated inflammation,including Toll-like receptors(TLRs),nucleotide-binding oligomerization domain(NOD)-like receptors(NLRs),RIG-I-like receptors(RLRs),C-type lectin receptors(CLRs)and the receptor for advanced glycation end products(RAGE).Herein,we summarized the physiological and pathological roles of E3 ligases in macrophage-mediated inflammation,as well as the inhibitors and agonists targeting E3 ligases in macrophage mediated inflammation,providing the new ideas for targeted therapies in macrophage-mediated inflammation caused aberrant function of E3 ligases.展开更多
Bivalve aquaculture plays a crucial role in the aquaculture industry due to the economic value of many bivalve species.Understanding the underlying genetic basis of bivalve growth regulation is essential for enhancing...Bivalve aquaculture plays a crucial role in the aquaculture industry due to the economic value of many bivalve species.Understanding the underlying genetic basis of bivalve growth regulation is essential for enhancing germplasm innovation and ensuring sustainable development of the industry.Though numerous candidate genes have been identified,their functional validation remains challenging.Fortunately,the dwarf surf clam(Mulinia lateralis)serves as a promising model organism for investigating genetic mechanisms underlying growth regulation in bivalves.The GWAS study in the Yesso scallop(Patinopecten yessoensis)has pinpointed the E2F3 gene as a key regulator of growth-related traits.However,the specific role of E2F3 in bivalve growth remains unclear.This study aimed to further confirm the regulatory function of the E2F3 gene in the dwarf surf clam through RNA interference experiments.Our results revealed several genes are associated with individual growth and development,including CTS7,HSP70B2,and PGLYRP3,as well as genes involved in lipid metabolism such as FABP2 and FASN.Functional enrichment analysis indicated that E2F3 primarily modulates critical processes like amino acid and lipid metabolism.These findings suggest that E2F3 likely regulates growth in the dwarf surf clam by influencing amino acid and lipid metabolism.Overall,this study advances our understanding on the function of E2F3 gene in growth regulation in bivalves,providing valuable insights for future research in this field.展开更多
文摘BACKGROUND Angelman syndrome(AS)is caused by maternal chromosomal deletions,imprinting defects,paternal uniparental disomy involving chromosome 15 and the ubiquitin-protein ligase UBE3A gene mutations.However the genetic basis remains unclear for several patients.AIM To investigate the involvement of UBE3A gene in AS and identifying new potential genes using exome sequencing.METHODS We established a cohort study in 50 patients referred to Farhat Hached University Hospital between 2006 and 2021,with a strong suspicion of AS and absence of chromosomal aberrations.The UBE3A gene was screened for mutation detection.Two unrelated patients issued from consanguineous families were subjected to exome analysis.RESULTS We describe seven UBE3A variants among them 3 none previously described including intronic variants c.2220+14T>C(intron14),c.2507+43T>A(Exon15)and insertion in Exon7:c.30-47_30-46.The exome sequencing revealed 22 potential genes that could be involved in AS-like syndromes that should be investigated further.CONCLUSION Screening for UBE3A mutations in AS patients has been proven to be useful to confirm the diagnosis.Our exome findings could rise to new potential alternative target genes for genetic counseling.
文摘Macrophages,existed in almost all organs of the body,are responsible for detecting tissue injury,pathogens,playing a key role in host defense against a variety of invading pathogens triggering inflammatory responses.Emerging evidence suggests that macrophage-mediated immune responses are efficiently regulated by the ubiquitination modification,which is responsible for normal immune responses.However,numerous studies indicates that the aberrant activation or inhibition of macrophage-mediated immune responses occurs in inflammation,mainly caused by dysregulated ubiquitination modification due to E3 ubiquitin ligases mutations or abnormal expression.Notably,E3 ubiquitin ligases,responsible for recognizing the substrates,are key enzymes in the ubiquitin proteasome system(UPS)composed of ubiquitin(Ub),ubiquitin-activating E1 enzymes,ubiquitin-conjugating E2 enzymes,E3 ubiquitin ligases,26S proteasome,and deubiquitinating enzymes.Intriguingly,several E3 ubiquitin ligases are involved in the regulation of some common signal pathways in macrophage-mediated inflammation,including Toll-like receptors(TLRs),nucleotide-binding oligomerization domain(NOD)-like receptors(NLRs),RIG-I-like receptors(RLRs),C-type lectin receptors(CLRs)and the receptor for advanced glycation end products(RAGE).Herein,we summarized the physiological and pathological roles of E3 ligases in macrophage-mediated inflammation,as well as the inhibitors and agonists targeting E3 ligases in macrophage mediated inflammation,providing the new ideas for targeted therapies in macrophage-mediated inflammation caused aberrant function of E3 ligases.
基金funded by the National Natural Science Foundation of China(No.U2106231)the Key Research and Development Project of Shandong Province(No.2021 ZLGX03)+1 种基金the National Key Research and Development Program of China(No.2022YFD2400303)supported by the High-Performance Computing Platform of YZBSTCACC.
文摘Bivalve aquaculture plays a crucial role in the aquaculture industry due to the economic value of many bivalve species.Understanding the underlying genetic basis of bivalve growth regulation is essential for enhancing germplasm innovation and ensuring sustainable development of the industry.Though numerous candidate genes have been identified,their functional validation remains challenging.Fortunately,the dwarf surf clam(Mulinia lateralis)serves as a promising model organism for investigating genetic mechanisms underlying growth regulation in bivalves.The GWAS study in the Yesso scallop(Patinopecten yessoensis)has pinpointed the E2F3 gene as a key regulator of growth-related traits.However,the specific role of E2F3 in bivalve growth remains unclear.This study aimed to further confirm the regulatory function of the E2F3 gene in the dwarf surf clam through RNA interference experiments.Our results revealed several genes are associated with individual growth and development,including CTS7,HSP70B2,and PGLYRP3,as well as genes involved in lipid metabolism such as FABP2 and FASN.Functional enrichment analysis indicated that E2F3 primarily modulates critical processes like amino acid and lipid metabolism.These findings suggest that E2F3 likely regulates growth in the dwarf surf clam by influencing amino acid and lipid metabolism.Overall,this study advances our understanding on the function of E2F3 gene in growth regulation in bivalves,providing valuable insights for future research in this field.
