RNA modifications have emerged as a dynamic and rapidly evolving field in the life sciences,captivating the attention of researchers worldwide due to their profound implications in diverse biological processes and dis...RNA modifications have emerged as a dynamic and rapidly evolving field in the life sciences,captivating the attention of researchers worldwide due to their profound implications in diverse biological processes and disease mechanisms.This special issue aims to compile a comprehensive array of cutting-edge research papers that delve into the multifaceted roles of RNA modifications,offering novel insights and advancing our understanding of this intricate regulatory layer.展开更多
Dysregulation of RNA N~6-methyladenosine(m~6A) modification in intestinal epithelial cells(IECs) compromises intestinal homeostasis,which is critical for maintaining gastrointestinal functions,immunity,and barrier int...Dysregulation of RNA N~6-methyladenosine(m~6A) modification in intestinal epithelial cells(IECs) compromises intestinal homeostasis,which is critical for maintaining gastrointestinal functions,immunity,and barrier integrity in inflammatory bowel disease(IBD).Here we explored the role of m~6A modification,particularly through methyltransferase like 3(METTL3),in IBD pathology and the apoptosis of intestinal stem cells(ISCs).Reduced m~6A RNA methylation and METTL3 expression were detected in IBD tissues,which correlated with increased ISC apoptosis and spontaneous enteritis in METTL3-deficient models;mechanistically,Mettl3 depletion increased TRADD expression in a m~6A dependent manner,thereby augmenting the TNF-induced apoptosis pathway,whereas pharmacological inhibition of TRADD ameliorated the apoptotic phenotype in METTL3-deficient models and improved survival rates in the enteritis mouse model,suggesting a novel therapeutic avenue for IBD management.Collectively,METTL3-mediated m~6A RNA methylation plays a pivotal role in maintaining intestinal homeostasis and is activated in ISCs to mitigate the hyperactivity of endogenous inflammatory signals;by modulating TRADD transcript metabolism,METTL3 limits excessive ISC apoptosis,providing insights into IBD pathogenesis and treatment strategies.展开更多
N^(6)-methyladenosine(m^(6)A)in RNA within R-loops plays pivotal roles in transcription regulation and genome stability.However,the precise impacts and distinct mechanisms of m^(6)A on both regulatory and aberrant R-l...N^(6)-methyladenosine(m^(6)A)in RNA within R-loops plays pivotal roles in transcription regulation and genome stability.However,the precise impacts and distinct mechanisms of m^(6)A on both regulatory and aberrant R-loops remain poorly understood.Here,we reveal that METTL3,the nuclear m^(6)A writer,ensures genome integrity by differentially modulating R-loops in a position-and length-dependent manner.In mouse embryonic stem cells(m ESCs),Mettl3 depletion results in impaired cell proliferation and increased cell death due to excessive DNA damage.Notably,Mettl3 knockout reduces the overall abundance of R-loops,with a decrease in broad R-loops and an increase in sharp Rloops.R-loops are diminished near transcription end sites(TESs),leading to transcriptional readthrough of genes with m^(6)A-modified transcripts and potentially contributing to genome instability.Conversely,increased sharp R-loops located in the antisense orientation relative to gene transcription are associated with DNA damage hotspots.These findings unveil a dual regulatory mechanism in which METTL3-m^(6)A orchestrates transcription fidelity and genome stability through distinct R-loop-dependent manners.展开更多
On January 22,2020,China National Center for Bioinformation(CNCB)released the 2019 Novel Coronavirus Resource(2019nCoVR),an open-access information resource for the severe acute respiratory syndrome coronavirus 2(SARS...On January 22,2020,China National Center for Bioinformation(CNCB)released the 2019 Novel Coronavirus Resource(2019nCoVR),an open-access information resource for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).2019nCoVR features a comprehensive integration of sequence and clinical information for all publicly available SARS-CoV-2 isolates,which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline.Of particular note,2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale.It provides all identified variants and their detailed statistics for each virus isolate,and congregates the quality score,functional annotation,and population frequency for each variant.Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available.Moreover,2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019(COVID-19),including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC.Furthermore,by linking with relevant databases in CNCB,2019nCoVR offers data submission services for raw sequence reads and assembled genomes,and data sharing with NCBI.Collectively,SARS-CoV-2 is updated daily to collect the latest information on genome sequences,variants,haplotypes,and literature for a timely reflection,making 2019nCoVR a valuable resource for the global research community.2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.展开更多
文摘RNA modifications have emerged as a dynamic and rapidly evolving field in the life sciences,captivating the attention of researchers worldwide due to their profound implications in diverse biological processes and disease mechanisms.This special issue aims to compile a comprehensive array of cutting-edge research papers that delve into the multifaceted roles of RNA modifications,offering novel insights and advancing our understanding of this intricate regulatory layer.
基金supported by the National Natural Science Foundation of China (81873555,32121001)Strategic Priority Research Program of the Chinese Academy of Science (XDB0570101600)Beijing Natural Science Foundation (Z200023,L244023)。
文摘Dysregulation of RNA N~6-methyladenosine(m~6A) modification in intestinal epithelial cells(IECs) compromises intestinal homeostasis,which is critical for maintaining gastrointestinal functions,immunity,and barrier integrity in inflammatory bowel disease(IBD).Here we explored the role of m~6A modification,particularly through methyltransferase like 3(METTL3),in IBD pathology and the apoptosis of intestinal stem cells(ISCs).Reduced m~6A RNA methylation and METTL3 expression were detected in IBD tissues,which correlated with increased ISC apoptosis and spontaneous enteritis in METTL3-deficient models;mechanistically,Mettl3 depletion increased TRADD expression in a m~6A dependent manner,thereby augmenting the TNF-induced apoptosis pathway,whereas pharmacological inhibition of TRADD ameliorated the apoptotic phenotype in METTL3-deficient models and improved survival rates in the enteritis mouse model,suggesting a novel therapeutic avenue for IBD management.Collectively,METTL3-mediated m~6A RNA methylation plays a pivotal role in maintaining intestinal homeostasis and is activated in ISCs to mitigate the hyperactivity of endogenous inflammatory signals;by modulating TRADD transcript metabolism,METTL3 limits excessive ISC apoptosis,providing insights into IBD pathogenesis and treatment strategies.
基金supported by the National Key Research and Development Program of China(2024YFA1802100)the Strategic Priority Research Program of Chinese Academy of Sciences(XDB0570101)+5 种基金the National Natural Science Foundation of China(32370644,32121001)the National Key Research and Development Program of China(2024YFC3405901,2020YFA0803401)the Key Research Program of Frontier Sciences,Chinese Academy of Sciences(ZDBS-LYSM013)Beijing Natural Science Foundation(L244023)Next-Generation Bioinformatics Algorithms(XDA0460302)CAS Youth Interdisciplinary Team。
文摘N^(6)-methyladenosine(m^(6)A)in RNA within R-loops plays pivotal roles in transcription regulation and genome stability.However,the precise impacts and distinct mechanisms of m^(6)A on both regulatory and aberrant R-loops remain poorly understood.Here,we reveal that METTL3,the nuclear m^(6)A writer,ensures genome integrity by differentially modulating R-loops in a position-and length-dependent manner.In mouse embryonic stem cells(m ESCs),Mettl3 depletion results in impaired cell proliferation and increased cell death due to excessive DNA damage.Notably,Mettl3 knockout reduces the overall abundance of R-loops,with a decrease in broad R-loops and an increase in sharp Rloops.R-loops are diminished near transcription end sites(TESs),leading to transcriptional readthrough of genes with m^(6)A-modified transcripts and potentially contributing to genome instability.Conversely,increased sharp R-loops located in the antisense orientation relative to gene transcription are associated with DNA damage hotspots.These findings unveil a dual regulatory mechanism in which METTL3-m^(6)A orchestrates transcription fidelity and genome stability through distinct R-loop-dependent manners.
基金This work was supported by grants from the Strategic PriorityResearch Program of Chinese Academy of Sciences(GrantNos.XDA19090116,XDA19050302,and XDB38030400)awarded to SS,ZZ,and MLthe National Key R&D Programof China(Grant Nos.2020YFC0848900,2020YFC0847000,2016YFE0206600,and 2017YFC0907502)+5 种基金the 13th Five-yearInformatization Plan of Chinese Academy of Sciences(GrantNo.XXH13505-05)Genomics Data Center Construction ofChinese Academy of Sciences(Grant No.XXH-13514-0202)the Open Biodiversity and Health Big Data Programme ofInternational Union of Biological Sciences,International Part-nership Program of Chinese Academy of Sciences(Grant No.153F11KYSB20160008)the Professional Association of theAlliance of International Science Organizations(Grant No.ANSO-PA-2020-07)This work was also supported by KCWong Education Foundation to ZZthe YouthInnovation Promotion Association of Chinese Academy ofSciences(Grant Nos.2017141 and 2019104)awarded to SSand ML.
文摘On January 22,2020,China National Center for Bioinformation(CNCB)released the 2019 Novel Coronavirus Resource(2019nCoVR),an open-access information resource for the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).2019nCoVR features a comprehensive integration of sequence and clinical information for all publicly available SARS-CoV-2 isolates,which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline.Of particular note,2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale.It provides all identified variants and their detailed statistics for each virus isolate,and congregates the quality score,functional annotation,and population frequency for each variant.Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available.Moreover,2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019(COVID-19),including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC.Furthermore,by linking with relevant databases in CNCB,2019nCoVR offers data submission services for raw sequence reads and assembled genomes,and data sharing with NCBI.Collectively,SARS-CoV-2 is updated daily to collect the latest information on genome sequences,variants,haplotypes,and literature for a timely reflection,making 2019nCoVR a valuable resource for the global research community.2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.
