The pathways leading to synthesis and post-synthetic modification of DNA employed methionine as donor of atoms: the carbon that came from its –CH3 served for DNA replication and repair either in bacteria or humans;it...The pathways leading to synthesis and post-synthetic modification of DNA employed methionine as donor of atoms: the carbon that came from its –CH3 served for DNA replication and repair either in bacteria or humans;its entire –CH3 served instead for building N6-methyladenine and 5-methylcytosine on bacterial DNA and 5-methylcytosine alone on human DNA. In humans, although a slight extra-S asymmetric methylation appeared de novo yielding on parental DNA 5’-m5CpC-3’/ 3’-GpG-5’, 5’-m5CpT-3’/3’-GpA-5’ and 5’-m5CpA-3’/3’-GpT-5’ monomethylated dinucleotide pairs, a heavy symmetric methylation involved in S semiconservatively newly made DNA to guarantee genetic maintenance of –CH3 in 5’-m5CpG-3’/3’-Gpm5C-5’ dimethylated dinucleotide pairs. In this framework, an inverse correlation was found between bulk genomic DNA methylation occurring in S and bulk polyA-containing pre-mRNA transcription taking place in G1 and G2. Thus, probes of 1 × 106 Daltons (constructed using sheared by sonication newly made methylated DNA filaments) revealed a modular organization in genes: after the hypermethylated promoter, they exhibited an alternation of unmethylated coding and methylated uncoding sequences. This encouraged the search for a language that genes regulated by methylation should have in common. An initial deciphering of restriction minimaps with hypomethylatable exons vs. hypermethylatable promoters and introns was improved when the bisulfite technique allowed a direct sequencing of m5C. In lymphocytes, where the transglutaminase gene is inactive, its promoter exhibited two fully methylated CpG-rich domains at 5’ and one fully unmethylated CpG-rich domain at 3’, including the site +1 and a 5’-UTR. At variance, in HUVEC cells, where the transglutaminase gene is active, in the first CpG-rich domain of promoter few doublets lost their –CH3. Such an inverse correlation suggested new hypotheses especially in connection with repair-modification: UV radiation would cause demethylation in given loci of a promoter by chance, whilst even a partial demethylation in this promoter would be able to resume a previously silent pre-mRNA transcription.展开更多
Long non-coding RNA (lncRNA) refers to an over 200 nt functional RNA molecule that will not be translated into protein. Previously thought to be dark matters of the genome, lncRNAs have been gradually recognized as cr...Long non-coding RNA (lncRNA) refers to an over 200 nt functional RNA molecule that will not be translated into protein. Previously thought to be dark matters of the genome, lncRNAs have been gradually recognized as crucial gene regulators. Although tremendous progress has been made in animals and human, the study of lncRNAs in plant is still in its infancy. Here, we reviewed the biogenesis and regulation mechanisms of lncRNAs and summarized the achievements that have been made in plant lncRNA identification and functional characterization. Genome-wide identification has uncovered large amount of lncRNAs in Arabidopsis, Rice, Maize and Wheat, and more information from other plant species will be expected with the aid of deep sequencing technologies. Similar to other species, LncRNA-mediated gene regulation also widely exists in plants, even though only a few functionally characterized examples are available. Up to now, at least four divergent lncRNA-mediated regulation mechanisms have been unraveled, including target mimicry, transcription interference, PRC2 associated histone methylation and DNA methylation. lncRNAs may be involved in the regulation of flowering, male sterility, nutrition metabolism, biotic and abiotic stress response in plants.展开更多
Objective This article aims to review recent studies on the biological characteristics of long non-coding RNAs （IncRNAs）, transcription regulation by IncRNAs, and the results of recent studies on the mechanism of ac...Objective This article aims to review recent studies on the biological characteristics of long non-coding RNAs （IncRNAs）, transcription regulation by IncRNAs, and the results of recent studies on the mechanism of action of IncRNAs in tumor development. Data sources The data cited in this review were mainly obtained from the articles listed in PubMed and HighWire that were published from January 2002 to June 2010. The search terms were ＂long non-coding RNA＂, ＂gene regulation＂, and ＂tumor＂. Study selection The mechanism of IncRNAs in gene expression regulation, and tumors concerned with IncRNAs and the role of IncRNAs in oncogenesis. Results IncRNAs play an important role in transcription control, and post-transcriptional controlling. IncRNAs are suppressing and promoting factors. regulation by controlling chromatin remodeling, transcriptional involved in many kinds of tumors and play key roles as both Conclusion IncRNAs could perfectly regulate the balance of gene expression system and play important roles in oncogenic cellular transformation.展开更多
Large scale cDNA sequencing and genome tiling array studies have shown that around 50% of genomic DNA in humans is transcribed, of which 2% is translated into proteins and the remaining 98% is non-coding RNAs (ncRNAs)...Large scale cDNA sequencing and genome tiling array studies have shown that around 50% of genomic DNA in humans is transcribed, of which 2% is translated into proteins and the remaining 98% is non-coding RNAs (ncRNAs). There is mounting evidence that these ncRNAs play critical roles in regulating DNA structure, RNA expression, protein translation and protein functions through multiple genetic mechanisms, and thus affect normal development of organisms at all levels. Today, we know very little about the regulatory mechanisms and functions of these ncRNAs, which is clearly essential knowledge for understanding the secret of life. To promote this emerging research subject of critical importance, in this paper we review (1) ncRNAs' past and present, (2) regulatory mechanisms and their functions, (3) experimental strategies for identifying novel ncRNAs, (4) experimental strategies for investigating their functions, and (5) methodologies and examples of the application of ncRNAs.展开更多
BACKGROUND Statistics indicate that the incidence of Crohn’s disease(CD)is rising in many countries.The poor understanding on the pathological mechanism has limited the development of effective therapy against this d...BACKGROUND Statistics indicate that the incidence of Crohn’s disease(CD)is rising in many countries.The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease.Previous studies showed that long noncoding RNAs(lncRNAs)could be involved in autoimmune diseases including CD,but the detailed molecular mechanisms remain unclear.AIM To identify the differentially expressed lncRNAs in the intestinal mucosa associated with CD,and to characterize their pathogenic role(s)and related mechanisms.METHODS The differential expression of lncRNAs was screened by high-throughput RNA sequencing,and the top candidate genes were validated in an expanded cohort by real-time PCR.The regulatory network was predicted by bioinformatic software and competitive endogenous RNA analysis,and was characterized in Caco-2 and HT-29 cell culture using methods of cell transfection,real-time PCR,Western blotting analysis,flow cytometry,and cell migration and invasion assays.Finally,these findings were confirmed in vivo using a CD animal model.RESULTS The 3'end of lncRNACNN3-206 and the 3’UTR of Caspase10 contain highaffinity miR212 binding sites.lncRNACNN3-206 expression was found to be significantly increased in intestinal lesions of CD patients.Activation of the lncRNACNN3-206-miR-212-Caspase10 regulatory network led to increased apoptosis,migration and invasion in intestinal epithelial cells.Knockdown of lncRNACNN3-206 expression alleviated intestinal mucosal inflammation and tissue damage in the CD mouse model.CONCLUSION lncRNACNN3-206 may play a key role in CD pathogenesis.lncRNACNN3-206 could be a therapeutic target for CD treatment.展开更多
文摘The pathways leading to synthesis and post-synthetic modification of DNA employed methionine as donor of atoms: the carbon that came from its –CH3 served for DNA replication and repair either in bacteria or humans;its entire –CH3 served instead for building N6-methyladenine and 5-methylcytosine on bacterial DNA and 5-methylcytosine alone on human DNA. In humans, although a slight extra-S asymmetric methylation appeared de novo yielding on parental DNA 5’-m5CpC-3’/ 3’-GpG-5’, 5’-m5CpT-3’/3’-GpA-5’ and 5’-m5CpA-3’/3’-GpT-5’ monomethylated dinucleotide pairs, a heavy symmetric methylation involved in S semiconservatively newly made DNA to guarantee genetic maintenance of –CH3 in 5’-m5CpG-3’/3’-Gpm5C-5’ dimethylated dinucleotide pairs. In this framework, an inverse correlation was found between bulk genomic DNA methylation occurring in S and bulk polyA-containing pre-mRNA transcription taking place in G1 and G2. Thus, probes of 1 × 106 Daltons (constructed using sheared by sonication newly made methylated DNA filaments) revealed a modular organization in genes: after the hypermethylated promoter, they exhibited an alternation of unmethylated coding and methylated uncoding sequences. This encouraged the search for a language that genes regulated by methylation should have in common. An initial deciphering of restriction minimaps with hypomethylatable exons vs. hypermethylatable promoters and introns was improved when the bisulfite technique allowed a direct sequencing of m5C. In lymphocytes, where the transglutaminase gene is inactive, its promoter exhibited two fully methylated CpG-rich domains at 5’ and one fully unmethylated CpG-rich domain at 3’, including the site +1 and a 5’-UTR. At variance, in HUVEC cells, where the transglutaminase gene is active, in the first CpG-rich domain of promoter few doublets lost their –CH3. Such an inverse correlation suggested new hypotheses especially in connection with repair-modification: UV radiation would cause demethylation in given loci of a promoter by chance, whilst even a partial demethylation in this promoter would be able to resume a previously silent pre-mRNA transcription.
文摘Long non-coding RNA (lncRNA) refers to an over 200 nt functional RNA molecule that will not be translated into protein. Previously thought to be dark matters of the genome, lncRNAs have been gradually recognized as crucial gene regulators. Although tremendous progress has been made in animals and human, the study of lncRNAs in plant is still in its infancy. Here, we reviewed the biogenesis and regulation mechanisms of lncRNAs and summarized the achievements that have been made in plant lncRNA identification and functional characterization. Genome-wide identification has uncovered large amount of lncRNAs in Arabidopsis, Rice, Maize and Wheat, and more information from other plant species will be expected with the aid of deep sequencing technologies. Similar to other species, LncRNA-mediated gene regulation also widely exists in plants, even though only a few functionally characterized examples are available. Up to now, at least four divergent lncRNA-mediated regulation mechanisms have been unraveled, including target mimicry, transcription interference, PRC2 associated histone methylation and DNA methylation. lncRNAs may be involved in the regulation of flowering, male sterility, nutrition metabolism, biotic and abiotic stress response in plants.
文摘Objective This article aims to review recent studies on the biological characteristics of long non-coding RNAs （IncRNAs）, transcription regulation by IncRNAs, and the results of recent studies on the mechanism of action of IncRNAs in tumor development. Data sources The data cited in this review were mainly obtained from the articles listed in PubMed and HighWire that were published from January 2002 to June 2010. The search terms were ＂long non-coding RNA＂, ＂gene regulation＂, and ＂tumor＂. Study selection The mechanism of IncRNAs in gene expression regulation, and tumors concerned with IncRNAs and the role of IncRNAs in oncogenesis. Results IncRNAs play an important role in transcription control, and post-transcriptional controlling. IncRNAs are suppressing and promoting factors. regulation by controlling chromatin remodeling, transcriptional involved in many kinds of tumors and play key roles as both Conclusion IncRNAs could perfectly regulate the balance of gene expression system and play important roles in oncogenic cellular transformation.
基金support by the National Natural Science Foundation of China(Grant No.30571517)National Transgenic Plants and Industria--lization Program(Grant Nos.J2002-B-005&JY03-B-28-02)National Key Basic Research Program("973")(Grant No.G1999016003).
文摘Large scale cDNA sequencing and genome tiling array studies have shown that around 50% of genomic DNA in humans is transcribed, of which 2% is translated into proteins and the remaining 98% is non-coding RNAs (ncRNAs). There is mounting evidence that these ncRNAs play critical roles in regulating DNA structure, RNA expression, protein translation and protein functions through multiple genetic mechanisms, and thus affect normal development of organisms at all levels. Today, we know very little about the regulatory mechanisms and functions of these ncRNAs, which is clearly essential knowledge for understanding the secret of life. To promote this emerging research subject of critical importance, in this paper we review (1) ncRNAs' past and present, (2) regulatory mechanisms and their functions, (3) experimental strategies for identifying novel ncRNAs, (4) experimental strategies for investigating their functions, and (5) methodologies and examples of the application of ncRNAs.
基金Supported by Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.KYCX18_0174
文摘BACKGROUND Statistics indicate that the incidence of Crohn’s disease(CD)is rising in many countries.The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease.Previous studies showed that long noncoding RNAs(lncRNAs)could be involved in autoimmune diseases including CD,but the detailed molecular mechanisms remain unclear.AIM To identify the differentially expressed lncRNAs in the intestinal mucosa associated with CD,and to characterize their pathogenic role(s)and related mechanisms.METHODS The differential expression of lncRNAs was screened by high-throughput RNA sequencing,and the top candidate genes were validated in an expanded cohort by real-time PCR.The regulatory network was predicted by bioinformatic software and competitive endogenous RNA analysis,and was characterized in Caco-2 and HT-29 cell culture using methods of cell transfection,real-time PCR,Western blotting analysis,flow cytometry,and cell migration and invasion assays.Finally,these findings were confirmed in vivo using a CD animal model.RESULTS The 3'end of lncRNACNN3-206 and the 3’UTR of Caspase10 contain highaffinity miR212 binding sites.lncRNACNN3-206 expression was found to be significantly increased in intestinal lesions of CD patients.Activation of the lncRNACNN3-206-miR-212-Caspase10 regulatory network led to increased apoptosis,migration and invasion in intestinal epithelial cells.Knockdown of lncRNACNN3-206 expression alleviated intestinal mucosal inflammation and tissue damage in the CD mouse model.CONCLUSION lncRNACNN3-206 may play a key role in CD pathogenesis.lncRNACNN3-206 could be a therapeutic target for CD treatment.
