Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcri...Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.展开更多
Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs （IncRNAs）. Emerging evidence indicates that IncRNAs may serve as master gene regulators through...Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs （IncRNAs）. Emerging evidence indicates that IncRNAs may serve as master gene regulators through various mechanisms. Dysregulation of IncRNAs is often associated with a variety of human diseases including cancer. Of significant interest, recent studies suggest that IncRNAs participate in the p53 tumor suppressor regulatory network. In this review, we discuss how IncRNAs serve as p53 regulators or p53 effectors. Further characterization of these p53-associated IncRNAs in cancer will provide a better understanding of lncRNA- mediated gene regulation in the p53 pathway. As a result, IncRNAs may prove to be valuable biomarkers for cancer diagnosis or poten- tial targets for cancer therapy.展开更多
In vitro, mouse embryonic stem （ES） cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a ne...In vitro, mouse embryonic stem （ES） cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a neural fate. Previous studies have shown that the neural conversion of mouse ES cells includes both the participation of neural-specific transcription factors and the regulation of epigenetic modifications. However, the intracellular mechanism underlying this intrinsic transition still re- mains to be further elucidated. Herein, we describe a long intergenic non-coding RNA, LincRNA1230, which participates in the regulation of the neural lineage specification of mouse ES cells. The ectopic forced expression of LincRNAI230 dramatically inhibited mouse ES cells from adopting a neural cell fate, while LincRNA1230 knockdown promoted the conversion of mouse ES cells towards neural progenitors. Mechanistic studies have shown that LincRNA1230 inhibits the activation of early neural genes, such as Pax6 and Soxl, through the modulation of bivalent modifications （tri-methylation of histone3 lysine4 and his- tone3 lysine27） at the promoters of these genes. The interaction of LincRNA1230 with Wdr5 blocked the localization of Wdr5 at the promoters of early neural genes, thereby inhibiting the enrichment of H3K4me3 modifications at these loci. Collectively, these findings revealed a crucial role for LincRNA1230 in the regulation of the neural differentiation of mouse ES cells.展开更多
Understanding the subcellular localization of long non-coding RNAs(IncRNAs)is crucial for unraveling their functional mechanisms.While previous computational methods have made progress in predicting IncRNA subcellular...Understanding the subcellular localization of long non-coding RNAs(IncRNAs)is crucial for unraveling their functional mechanisms.While previous computational methods have made progress in predicting IncRNA subcellular localization,most of them ignore the sequence order information by relying on k-mer frequency features to encode IncRNA sequences.In the study,we develope SGCL-LncLoc,a novel interpretable deep learning model based on supervised graph contrastive learning.SGCL-LncLoc transforms IncRNA sequences into de Bruijn graphs and uses the Word2Vec technique to learn the node representation of the graph.Then,SGCL-LncLoc applies graph convolutional networks to learn the comprehensive graph representation.Additionally,we propose a computational method to map the attention weights of the graph nodes to the weights of nucleotides in the IncRNA sequence,allowing SGCL-LncLoc to serve as an interpretable deep learning model.Furthermore,SGCL-LncLoc employs a supervised contrastive learning strategy,which leverages the relationships between different samples and label information,guiding the model to enhance representation learning for IncRNAs.Extensive experimental results demonstrate that SGCL-LncLoc outperforms both deep learning baseline models and existing predictors,showing its capability for accurate IncRNA subcellular localization prediction.Furthermore,we conduct a motif analysis,revealing that SGCL-LncLoc successfully captures known motifs associated with IncRNA subcellular localization.The SGCL-LncLoc web server is available at http://csuligroup.com:8000/SGCL-LncLoc.The source code can be obtained from https://github.com/CSUBioGroup/SGCL-LncLoc.展开更多
m6A甲基化是mRNA和lncRNA等RNA分子中的一种重要表观遗传修饰,通过调控基因表达,在消化道肿瘤的发生和发展中发挥重要作用。m6A甲基化修饰的lncRNA对多种消化道肿瘤如肝癌、胃癌、食管癌和胰腺癌的增殖、侵袭及转移有显著影响。在消化...m6A甲基化是mRNA和lncRNA等RNA分子中的一种重要表观遗传修饰,通过调控基因表达,在消化道肿瘤的发生和发展中发挥重要作用。m6A甲基化修饰的lncRNA对多种消化道肿瘤如肝癌、胃癌、食管癌和胰腺癌的增殖、侵袭及转移有显著影响。在消化道肿瘤的诊断、治疗和预后评估中,m6A修饰的lncRNA作为生物标志物具有广泛应用潜力。未来的研究有望将这一修饰机制转化为临床治疗靶点,提升患者生存率和治疗效果。m6A methylation is an important epigenetic modification in RNA molecules such as mRNA and lncRNA, which plays an important role in the occurrence and development of gastrointestinal tumors by regulating gene expression. m6A methylation-modified lncRNA has a significant impact on the proliferation, invasion, and metastasis of a variety of gastrointestinal tract tumors such as hepatocellular carcinomas, gastric carcinomas, esophageal carcinomas, and pancreatic carcinomas. The m6A-modified lncRNA has a wide potential for use as biomarkers in the diagnosis, treatment and prognosis evaluation of GI tumors. Future studies are expected to translate this modification mechanism into clinical therapeutic targets to enhance patient survival and treatment effects.展开更多
文摘Once thought to be transcriptional noise, large non-coding RNAs （IncRNAs） have recently been demonstrated to be functional molecules. The cell-type-specific expression patterns of lncRNAs suggest that their transcription may be regulated epigenetically. Using a custom-designed microarray, here we examine the expression profile of IncRNAs in embryonic stem （ES） cells, lineage-restricted neuronal progenitor cells, and terminally differentiated fibroblasts. In addition, we also analyze the relationship between their expression and their promoter H3K4 and H3K27 methyla- tion patterns. We find that numerous lncRNAs in these cell types undergo changes in the levels of expression and promoter H3K4me3 and H3K27me3. Interestingly, lncRNAs that are expressed at lower levels in ES cells exhibit higher levels of H3K27me3 at their promoters. Consistent with this result, knockdown of the H3K27me3 methyltransferase Ezh2 results in derepression of these IncRNAs in ES cells. Thus, our results establish a role for Ezh2-mediated H3K27 methylation in lncRNA silencing in ES cells and reveal that lncRNAs are subject to epigenetic regulation in a similar manner to that of the protein-coding genes.
文摘Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs （IncRNAs）. Emerging evidence indicates that IncRNAs may serve as master gene regulators through various mechanisms. Dysregulation of IncRNAs is often associated with a variety of human diseases including cancer. Of significant interest, recent studies suggest that IncRNAs participate in the p53 tumor suppressor regulatory network. In this review, we discuss how IncRNAs serve as p53 regulators or p53 effectors. Further characterization of these p53-associated IncRNAs in cancer will provide a better understanding of lncRNA- mediated gene regulation in the p53 pathway. As a result, IncRNAs may prove to be valuable biomarkers for cancer diagnosis or poten- tial targets for cancer therapy.
基金supported by National Natural Science Foundation of China (81530042, 31571529, 31210103905, 31571519, 31571390, 31371510, 31301208, 31471250, 31401257)the Ministry of Science and Technology (2012CB966603, 2013CB967600, 2013CB967401)+2 种基金Science and Technology Commission of Shanghai Municipality (15JC1403200, 15JC1403201)Shanghai Rising-Star Program (14QA1403900)the Fundamental Research Funds for the Central Universities (2000219099)
文摘In vitro, mouse embryonic stem （ES） cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a neural fate. Previous studies have shown that the neural conversion of mouse ES cells includes both the participation of neural-specific transcription factors and the regulation of epigenetic modifications. However, the intracellular mechanism underlying this intrinsic transition still re- mains to be further elucidated. Herein, we describe a long intergenic non-coding RNA, LincRNA1230, which participates in the regulation of the neural lineage specification of mouse ES cells. The ectopic forced expression of LincRNAI230 dramatically inhibited mouse ES cells from adopting a neural cell fate, while LincRNA1230 knockdown promoted the conversion of mouse ES cells towards neural progenitors. Mechanistic studies have shown that LincRNA1230 inhibits the activation of early neural genes, such as Pax6 and Soxl, through the modulation of bivalent modifications （tri-methylation of histone3 lysine4 and his- tone3 lysine27） at the promoters of these genes. The interaction of LincRNA1230 with Wdr5 blocked the localization of Wdr5 at the promoters of early neural genes, thereby inhibiting the enrichment of H3K4me3 modifications at these loci. Collectively, these findings revealed a crucial role for LincRNA1230 in the regulation of the neural differentiation of mouse ES cells.
基金supported by the National Natural Science Foundation of China(No.62102457)the Hunan Provincial Natural Science Foundation of China(No.2023JJ40763)+1 种基金the Hunan Provincial Science and Technology Program(No.2021RC4008)the Fundamental Research Funds for the Central Universities of Central South University(No.CX20230271).
文摘Understanding the subcellular localization of long non-coding RNAs(IncRNAs)is crucial for unraveling their functional mechanisms.While previous computational methods have made progress in predicting IncRNA subcellular localization,most of them ignore the sequence order information by relying on k-mer frequency features to encode IncRNA sequences.In the study,we develope SGCL-LncLoc,a novel interpretable deep learning model based on supervised graph contrastive learning.SGCL-LncLoc transforms IncRNA sequences into de Bruijn graphs and uses the Word2Vec technique to learn the node representation of the graph.Then,SGCL-LncLoc applies graph convolutional networks to learn the comprehensive graph representation.Additionally,we propose a computational method to map the attention weights of the graph nodes to the weights of nucleotides in the IncRNA sequence,allowing SGCL-LncLoc to serve as an interpretable deep learning model.Furthermore,SGCL-LncLoc employs a supervised contrastive learning strategy,which leverages the relationships between different samples and label information,guiding the model to enhance representation learning for IncRNAs.Extensive experimental results demonstrate that SGCL-LncLoc outperforms both deep learning baseline models and existing predictors,showing its capability for accurate IncRNA subcellular localization prediction.Furthermore,we conduct a motif analysis,revealing that SGCL-LncLoc successfully captures known motifs associated with IncRNA subcellular localization.The SGCL-LncLoc web server is available at http://csuligroup.com:8000/SGCL-LncLoc.The source code can be obtained from https://github.com/CSUBioGroup/SGCL-LncLoc.
文摘m6A甲基化是mRNA和lncRNA等RNA分子中的一种重要表观遗传修饰,通过调控基因表达,在消化道肿瘤的发生和发展中发挥重要作用。m6A甲基化修饰的lncRNA对多种消化道肿瘤如肝癌、胃癌、食管癌和胰腺癌的增殖、侵袭及转移有显著影响。在消化道肿瘤的诊断、治疗和预后评估中,m6A修饰的lncRNA作为生物标志物具有广泛应用潜力。未来的研究有望将这一修饰机制转化为临床治疗靶点,提升患者生存率和治疗效果。m6A methylation is an important epigenetic modification in RNA molecules such as mRNA and lncRNA, which plays an important role in the occurrence and development of gastrointestinal tumors by regulating gene expression. m6A methylation-modified lncRNA has a significant impact on the proliferation, invasion, and metastasis of a variety of gastrointestinal tract tumors such as hepatocellular carcinomas, gastric carcinomas, esophageal carcinomas, and pancreatic carcinomas. The m6A-modified lncRNA has a wide potential for use as biomarkers in the diagnosis, treatment and prognosis evaluation of GI tumors. Future studies are expected to translate this modification mechanism into clinical therapeutic targets to enhance patient survival and treatment effects.
