Recently,small nucleolar RNAs(snoRNAs)have transcended the genomic“noise”to emerge as pivotal molecular markers due to their essential roles in tumor progression.Substantial evidence indicates a strong association b...Recently,small nucleolar RNAs(snoRNAs)have transcended the genomic“noise”to emerge as pivotal molecular markers due to their essential roles in tumor progression.Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance.Historically,snoRNA research has concentrated on two classical mechanisms:2'-O-ribose methylation and pseudouridylation.This review specifically summarizes the novel regulatory mechanisms and functional patterns of snoRNAs in tumors,encompassing transcriptional,post-transcriptional,and post-translational regulation.We further discuss the synergistic effect between snoRNA host genes(SNHGs)and snoRNAs in tumor progression.More importantly,snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes.Accordingly,we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.展开更多
Small nucleolar RNAs (snoRNAs) play an important role in eukaryotic rRNA biogenesis. By combination of a computer search of EMBL database and experimental procedure, a novel snoRNA coding sequence (Z8) was screened ou...Small nucleolar RNAs (snoRNAs) play an important role in eukaryotic rRNA biogenesis. By combination of a computer search of EMBL database and experimental procedure, a novel snoRNA coding sequence (Z8) was screened out and characterized from yeast Saccharomyces cerevisiae genome. Z8 snoRNA gene codes a boxC/D antisense snoRNA which guides, deduced from structure analysis, the 2'-0-ribose methylation at U2421 of 25S rRNA. After disruption of Z8 snoRNA gene, the methylation at corresponding site was abolished, but no growth delay was observed in various cultural temperatures. Z8 DNA is the first gene of a gene cluster consisting of three cognate snoRNA genes which are located on an intergenic region of chromosomeⅫⅠ. This gene cluster is co-transcribed as a polycistronic precursor from a + 247 bp U snoRNA gene promoter, followed by processing to release individual snoRNAs, representing a new expression pattern of snoRNA genes.展开更多
Small nucleolar RNAs(snoRNAs)were previously regarded as a class of functionally conserved housekeeping genes,primarily involved in the regulation of ribosome biogenesis by ribosomal RNA(rRNA)modification.However,some...Small nucleolar RNAs(snoRNAs)were previously regarded as a class of functionally conserved housekeeping genes,primarily involved in the regulation of ribosome biogenesis by ribosomal RNA(rRNA)modification.However,some of them are involved in several biological processes via complex molecular mechanisms.DNA damage response(DDR)is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases.It has recently been revealed that snoRNAs are involved in DDR at multiple levels,indicating their relevant theoretical and clinical significance in this field.The present review systematically addresses four main points,including the biosynthesis and classification of snoRNAs,the mechanisms through which snoRNAs regulate target molecules,snoRNAs in the process of DDR,and the significance of snoRNA in disease diagnosis and treatment.It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.展开更多
Background Subclinical mastitis,caused by many pathogens including Staphylococcus aureus(S.aureus)and Staphylococcus chromogenes(S.chromogenes),presents a major challenge to the dairy industry due to its associated ec...Background Subclinical mastitis,caused by many pathogens including Staphylococcus aureus(S.aureus)and Staphylococcus chromogenes(S.chromogenes),presents a major challenge to the dairy industry due to its associated economic losses and poor milk quality.The molecular regulatory mechanisms,including the role of small nucleolar RNAs(snoRNAs),of the host response to mastitis pathogens remain unclear.Therefore,this study investigated snoRNA expression and potential roles during subclinical mastitis.Milk somatic cells from cows with naturally occurring S.aureus(n=14)and S.chromogenes(n=3)subclinical mastitis,and healthy cows(n=4)were subjected to transcriptome sequencing and bioinformatics analyses.Results We identified 255 expressed snoRNAs including 21 differentially expressed(DE)in S.aureus-positive cows and 20 DE in S.chromogenes-positive cows.Prediction of ribosomal RNA(rRNA)modification sites found several 18S rRNA and 28S rRNA modification(pseudouridylation and 2′-O-methylation)target sites essential for ribosome function for DE snoRNAs,such as SNORA79(18S-1319,28S-3001),SNORA1(18S-1496,28S-1747),suggesting their roles in translation and immune modulation during subclinical mastitis.Correlation analysis identified DE snoRNAs-mRNAs(from the same samples)pairs with majority of the correlated mRNAs(e.g.,CXCL8,IL6R,IL2,IL1R,IL18R1,STAT3,NFKB2,MYD88,VEGFA,and CD40)having immune related functions.Functional enrichment of correlated genes of snoRNAs for S.aureus-positive group(regulation of defense/immune response,leukocyte differentiation,response to cytokine,NF-κB signaling pathway,JAK-STAT signaling pathway etc.)and S.chromogenes-positive group(e.g.,regulation of defense response,response to cytokine,regulation of immune response,NF-κB signaling pathway,TNF signaling pathway,and JAK-STAT signaling pathway)revealed involvement in immune and inflammatory processes.Some functional terms were common to both pathogens(e.g.,NF-κB,JAK-STAT signaling,immune system processes)and suggest common regulatory mechanisms used by both pathogens to contain infection.Furthermore,snoRNA-mRNA network construction identified 7 key(hub)snoRNAs each for S.aureus-positive group(SNORA66,novelsnoRNA_26_14905(also denoted as novelSnoRNA_86),SNORD107,SNORA1,SNORA63,SNORA79,SNORA76)and S.chromogenes-positive group(SNORD18,SNORA79,SNORA46,U2-19,SNORA66,SNORD37,SNORD49)that correlated with the most protein coding genes(|r|>0.9;≥30 mRNAs).Functional enrichment of correlated genes of hub snoRNAs reveals their involvement in immune related functions(75%of enriched terms)and metabolic processes(20%of enriched terms).Conclusion These data suggest potential regulatory roles for the DE snoRNAs and in particular,the 14 hub snoRNAs during subclinical mastitis.This study presents the first evidence linking snoRNAs to bovine subclinical mastitis and offers new insights into the molecular mechanisms underlying subclinical mastitis caused by S.aureus and S.chromogenes.展开更多
目的探讨snoRNA来源的piRNA在乳腺癌中对FOXO3a基因的影响。方法将5个化学合成的pi-snoRNAs(pi-sno44/74/75/78/81)分别转入MDA-MB-231乳腺癌细胞后收样提取总RNA,检测每个piRNA对FOXO3a m RNA水平的影响,找出对FOXO3a作用最明显的piRNA...目的探讨snoRNA来源的piRNA在乳腺癌中对FOXO3a基因的影响。方法将5个化学合成的pi-snoRNAs(pi-sno44/74/75/78/81)分别转入MDA-MB-231乳腺癌细胞后收样提取总RNA,检测每个piRNA对FOXO3a m RNA水平的影响,找出对FOXO3a作用最明显的piRNA,验证其对FOXO3a蛋白水平的影响;收集2016年3月~2016年10月在我科行乳腺根治手术的乳腺癌患者术后新鲜肿瘤及瘤旁标本28对,检测其中pi-sno81、sno81及FOXO3a的表达情况;应用典型相关分析对pi-sno81、sno81及FOXO3a在乳腺癌及癌旁乳腺组织中的表达情况进行相关性分析,了解pi-sno81与FOXO3a的相关性。结果 qRT-PCR检测发现,FOXO3a基因表达被pisno44/74/75/81上调;其中pi-sno81上调FOXO3a最明显,且pi-sno81明显上调了FOXO3a蛋白水平;FOXO3a在乳腺癌中呈低表达;相关性分析发现,pi-sno81在乳腺癌及癌旁乳腺组织中的表达与FOXO3a在乳腺癌及癌旁乳腺组织中的表达成正相关(P<0.001,Corr=0.835)。结论 snoRNA来源的pi-sno81能上调乳腺癌细胞中FOXO3a基因的表达,并可能通过影响FOXO3a的表达影响乳腺癌细胞的生长。展开更多
基金supported by grants from the National Natural Science Foundation of China(81872905,82272915,and 82073884)the Project of the Fourth Batch of Science and Technology Plan of Liaoning Province,China(Grant No.:2021JH210300133)+3 种基金Science and Technology Innovation Team Project of China Medical University,China(Grant No.:CXTD2022007)the Supporting the Highquality Development of Science and Technology Funding Projects at China Medical University(Grant No.:2022011963-JH2/202)China Postdoctoral Science Foundation(Grant No.:2023MD734246)Liaoning Province Natural Science Foundation Joint Fund(Grant No.:2023-MSLH-396)。
文摘Recently,small nucleolar RNAs(snoRNAs)have transcended the genomic“noise”to emerge as pivotal molecular markers due to their essential roles in tumor progression.Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance.Historically,snoRNA research has concentrated on two classical mechanisms:2'-O-ribose methylation and pseudouridylation.This review specifically summarizes the novel regulatory mechanisms and functional patterns of snoRNAs in tumors,encompassing transcriptional,post-transcriptional,and post-translational regulation.We further discuss the synergistic effect between snoRNA host genes(SNHGs)and snoRNAs in tumor progression.More importantly,snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes.Accordingly,we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.
基金This work was supported by the National Natural Science Foundation of China(Grant No.30230200)the Fund for Distinguished Young Scholars from the Ministry of Education of China.
基金Project supported by the National Natural Science Foundation of China (Grant No. 397303000)
文摘Small nucleolar RNAs (snoRNAs) play an important role in eukaryotic rRNA biogenesis. By combination of a computer search of EMBL database and experimental procedure, a novel snoRNA coding sequence (Z8) was screened out and characterized from yeast Saccharomyces cerevisiae genome. Z8 snoRNA gene codes a boxC/D antisense snoRNA which guides, deduced from structure analysis, the 2'-0-ribose methylation at U2421 of 25S rRNA. After disruption of Z8 snoRNA gene, the methylation at corresponding site was abolished, but no growth delay was observed in various cultural temperatures. Z8 DNA is the first gene of a gene cluster consisting of three cognate snoRNA genes which are located on an intergenic region of chromosomeⅫⅠ. This gene cluster is co-transcribed as a polycistronic precursor from a + 247 bp U snoRNA gene promoter, followed by processing to release individual snoRNAs, representing a new expression pattern of snoRNA genes.
基金supported by the National Natural Science Foundation of China(32071240,82373526).
文摘Small nucleolar RNAs(snoRNAs)were previously regarded as a class of functionally conserved housekeeping genes,primarily involved in the regulation of ribosome biogenesis by ribosomal RNA(rRNA)modification.However,some of them are involved in several biological processes via complex molecular mechanisms.DNA damage response(DDR)is a conserved mechanism for maintaining genomic stability to prevent the occurrence of various human diseases.It has recently been revealed that snoRNAs are involved in DDR at multiple levels,indicating their relevant theoretical and clinical significance in this field.The present review systematically addresses four main points,including the biosynthesis and classification of snoRNAs,the mechanisms through which snoRNAs regulate target molecules,snoRNAs in the process of DDR,and the significance of snoRNA in disease diagnosis and treatment.It focuses on the potential functions of snoRNAs in DDR to help in the discovery of the roles of snoRNAs in maintaining genome stability and pathological processes.
基金Agriculture and Agri-Food Canada funded this research(grant number J-002223).
文摘Background Subclinical mastitis,caused by many pathogens including Staphylococcus aureus(S.aureus)and Staphylococcus chromogenes(S.chromogenes),presents a major challenge to the dairy industry due to its associated economic losses and poor milk quality.The molecular regulatory mechanisms,including the role of small nucleolar RNAs(snoRNAs),of the host response to mastitis pathogens remain unclear.Therefore,this study investigated snoRNA expression and potential roles during subclinical mastitis.Milk somatic cells from cows with naturally occurring S.aureus(n=14)and S.chromogenes(n=3)subclinical mastitis,and healthy cows(n=4)were subjected to transcriptome sequencing and bioinformatics analyses.Results We identified 255 expressed snoRNAs including 21 differentially expressed(DE)in S.aureus-positive cows and 20 DE in S.chromogenes-positive cows.Prediction of ribosomal RNA(rRNA)modification sites found several 18S rRNA and 28S rRNA modification(pseudouridylation and 2′-O-methylation)target sites essential for ribosome function for DE snoRNAs,such as SNORA79(18S-1319,28S-3001),SNORA1(18S-1496,28S-1747),suggesting their roles in translation and immune modulation during subclinical mastitis.Correlation analysis identified DE snoRNAs-mRNAs(from the same samples)pairs with majority of the correlated mRNAs(e.g.,CXCL8,IL6R,IL2,IL1R,IL18R1,STAT3,NFKB2,MYD88,VEGFA,and CD40)having immune related functions.Functional enrichment of correlated genes of snoRNAs for S.aureus-positive group(regulation of defense/immune response,leukocyte differentiation,response to cytokine,NF-κB signaling pathway,JAK-STAT signaling pathway etc.)and S.chromogenes-positive group(e.g.,regulation of defense response,response to cytokine,regulation of immune response,NF-κB signaling pathway,TNF signaling pathway,and JAK-STAT signaling pathway)revealed involvement in immune and inflammatory processes.Some functional terms were common to both pathogens(e.g.,NF-κB,JAK-STAT signaling,immune system processes)and suggest common regulatory mechanisms used by both pathogens to contain infection.Furthermore,snoRNA-mRNA network construction identified 7 key(hub)snoRNAs each for S.aureus-positive group(SNORA66,novelsnoRNA_26_14905(also denoted as novelSnoRNA_86),SNORD107,SNORA1,SNORA63,SNORA79,SNORA76)and S.chromogenes-positive group(SNORD18,SNORA79,SNORA46,U2-19,SNORA66,SNORD37,SNORD49)that correlated with the most protein coding genes(|r|>0.9;≥30 mRNAs).Functional enrichment of correlated genes of hub snoRNAs reveals their involvement in immune related functions(75%of enriched terms)and metabolic processes(20%of enriched terms).Conclusion These data suggest potential regulatory roles for the DE snoRNAs and in particular,the 14 hub snoRNAs during subclinical mastitis.This study presents the first evidence linking snoRNAs to bovine subclinical mastitis and offers new insights into the molecular mechanisms underlying subclinical mastitis caused by S.aureus and S.chromogenes.
文摘目的探讨snoRNA来源的piRNA在乳腺癌中对FOXO3a基因的影响。方法将5个化学合成的pi-snoRNAs(pi-sno44/74/75/78/81)分别转入MDA-MB-231乳腺癌细胞后收样提取总RNA,检测每个piRNA对FOXO3a m RNA水平的影响,找出对FOXO3a作用最明显的piRNA,验证其对FOXO3a蛋白水平的影响;收集2016年3月~2016年10月在我科行乳腺根治手术的乳腺癌患者术后新鲜肿瘤及瘤旁标本28对,检测其中pi-sno81、sno81及FOXO3a的表达情况;应用典型相关分析对pi-sno81、sno81及FOXO3a在乳腺癌及癌旁乳腺组织中的表达情况进行相关性分析,了解pi-sno81与FOXO3a的相关性。结果 qRT-PCR检测发现,FOXO3a基因表达被pisno44/74/75/81上调;其中pi-sno81上调FOXO3a最明显,且pi-sno81明显上调了FOXO3a蛋白水平;FOXO3a在乳腺癌中呈低表达;相关性分析发现,pi-sno81在乳腺癌及癌旁乳腺组织中的表达与FOXO3a在乳腺癌及癌旁乳腺组织中的表达成正相关(P<0.001,Corr=0.835)。结论 snoRNA来源的pi-sno81能上调乳腺癌细胞中FOXO3a基因的表达,并可能通过影响FOXO3a的表达影响乳腺癌细胞的生长。
