上游开放阅读框(upstream open reading frame, uORF)是一类能够精确控制蛋白质翻译的mRNA元件,位于mRNA的5'端前导区,主要通过抑制翻译起始来调节下游主体开放阅读框(main open reading frame, mORF)的翻译。目前对植物uORF的预测...上游开放阅读框(upstream open reading frame, uORF)是一类能够精确控制蛋白质翻译的mRNA元件,位于mRNA的5'端前导区,主要通过抑制翻译起始来调节下游主体开放阅读框(main open reading frame, mORF)的翻译。目前对植物uORF的预测和鉴定主要集中于生物信息学和翻译组学鉴定技术。植物uORF广泛参与调节生长发育、营养代谢、抗病免疫等多个生命活动过程。本文对植物uORF的分类、功能机制、预测和鉴定方法、植物规避uORF的方式以及植物uORF的工程应用等进行综述归纳,旨在更系统和深入地理解植物uORF的功能与机制,并为uORF应用于作物分子育种工作提供参考。展开更多
Conventional peptides(CPs)and non-conventional peptides(NCPs)are generated from small open reading frames,but most CPs are derived from large precursors.NCPs,which are derived from sequences other than conventional op...Conventional peptides(CPs)and non-conventional peptides(NCPs)are generated from small open reading frames,but most CPs are derived from large precursors.NCPs,which are derived from sequences other than conventional open reading frames or annotated coding sequences regions,function in plant development and adaptation to stresses.Ribosome profiling,a technique for studying translational regulation,can be used to identify NCPs.Another new technique,peptidogenomics,which integrates mass spectrometry and genomics,is becoming more widely used for identifying plant NCPs.In recent years,numerous studies have investigated the roles in monocots and dicots of miRNA-derived peptides and upstream open reading frames,which have potential for improving agronomic traits.Investigating the biological functions of NCPs will advance molecular plant breeding by identifying regulators of plant growth and development.We present an overview of NCP identification methods and recent findings about NCP biological functions.展开更多
Research Aims: Obesity and type 2 diabetes are known to be associated with increased risk of various types of cancer. However, the molecular biological mechanism of how the risk of cancer is increased in obesity or ty...Research Aims: Obesity and type 2 diabetes are known to be associated with increased risk of various types of cancer. However, the molecular biological mechanism of how the risk of cancer is increased in obesity or type 2 diabetes is not known. The aim this research is to investigate if the decreased expression of p27Kip1, a cell cycle repressor protein, plays a central role in this mechanism. Research Methods, Previous Studies and Theoretical Backgrounds: It is well known that the expression of p27Kip1 is increased by numerous nutritional or chemopreventive anti-cancer agents. But it has never been known that the expression of p27Kip1 could be decreased, rather than increased, and the risk of cancer could be increased, rather than decreased. This problem was solved recently and this new analytical method was used in this study. Results: 1) The expression of p27Kip1 was indeed significantly decreased in human obese type 2 diabetic individuals relative to the lean normal controls. 2) The expression of p27Kip1 was also significantly decreased in genetically obese rodents relative to the lean normal controls. Additionally, in obese rodents, the concentrations of glucose or insulin were significantly increased relative to the lean normal controls. 3) Using human cells cultured in vitro it was found that the increased concentrations of glucose or insulin decrease the expression of p27Kip1. Conclusions: These results suggest that higher concentrations of glucose or insulin increase the risk of various types of cancer in obesity or type 2 diabetes by decreasing the expression of p27Kip1.展开更多
基因组中约有20%的基因具有上游开放阅读框(upstream open reading frame,uORF),它位于成熟mRNA 5'端非编码区(5'-UTR)。本文简介了uORF同源群的挖掘方法、分类和进化,以及调控下游mORF翻译的研究进展。植物(拟南芥和水稻等)和...基因组中约有20%的基因具有上游开放阅读框(upstream open reading frame,uORF),它位于成熟mRNA 5'端非编码区(5'-UTR)。本文简介了uORF同源群的挖掘方法、分类和进化,以及调控下游mORF翻译的研究进展。植物(拟南芥和水稻等)和昆虫(果蝇等)基因组中普遍存在保守肽uORFs,并且在序列多样性方面有相似之处。但它们在平均长度、基因组聚类、与甲基转移酶的关联性上有所不同。植物uORF的长度通常短于昆虫uORF。借助拟南芥和水稻全长cDNA序列比较,不同的uORF同源群对其下游如转录因子,信号转导因子、发育信号分子和翻译起始因子eIF5等编码基因的mORF具有调控功能。对于真核生物基因组中包含CHCH域的uORF进行贝叶斯系统发育分析,结果表明,同源群8-like分属5个物种(绿藻、节肢动物、线虫、无脊椎动物和真菌)。在真核生物生长、发育和生理过程中,uORF通常作为反式因子对mORF表达起调节器作用,例如,在植物蔗糖、多胺、磷脂酰胆碱,以及甲基转移酶反应中,相当大比例的uORF参与介导mORF的翻译调控。展开更多
Messenger RNA(mRNA)translation consists of initiation,elongation,termination,and ribosome recycling,carried out by the translation machinery,primarily including tRNAs,ribosomes,and translation factors(TrFs).Translatio...Messenger RNA(mRNA)translation consists of initiation,elongation,termination,and ribosome recycling,carried out by the translation machinery,primarily including tRNAs,ribosomes,and translation factors(TrFs).Translational regulators transduce signals of growth and development,as well as biotic and abiotic stresses,to the translation machinery,where global or selective translational control occurs to modulate mRNA translation efficiency(TrE).As the basis of translational control,the translation machinery directly determines the quality and quantity of newly synthesized peptides and,ultimately,the cellular adaption.Thus,regulating the availability of diverse machinery components is reviewed as the central strategy of translational control.We provide classical signaling pathways(e.g.,integrated stress responses)and cellular behaviors(e.g.,liquideliquid phase separation)to exemplify this strategy within different physiological contexts,particularly during hostemicrobe interactions.With new technologies developed,further understanding this strategy will speed up translational medicine and translational agriculture.展开更多
A 5'-leader,known initially as the 5'-untranslated region,contains multiple isoforms due to alternative splicing(aS)and alternative transcription start site(aTSS).Therefore,a representative 5'-leader is de...A 5'-leader,known initially as the 5'-untranslated region,contains multiple isoforms due to alternative splicing(aS)and alternative transcription start site(aTSS).Therefore,a representative 5'-leader is demanded to examine the embedded RNA regulatory elements in controlling translation efficiency.Here,we develop a ranking algorithm and a deep-learning model to annotate representative 5'-leaders for five plant species.We rank the intra-sample and inter-sample frequency of aS-mediated transcript isoforms using the Kruskal-Wallis test-based algorithm and identify the representative aS-5'-leader.To further assign a representative 5'-end,we train the deep-learning model 5'leaderP to learn aTsS-mediated 5'-end distribution patterns from cap-analysis gene expression data.The model accurately predicts the 5'-end,confirmed experimentally in Arabidopsis and rice.The representative 5'-leader-contained gene models and 5'leaderP can be accessed at RNAirport(http:/www.rnairport.com/leader5P/).The Stage 1 annotation of 5'-leader records 5'-leader diversity and will pave the way to Ribo-Seq open-reading frame annotation,identical to the project recently initiated by human GENCODE.展开更多
小开放阅读框(small open reading frame,sORF)广泛存在于不同生物基因组中,由于其序列短,以及编码的产物小蛋白(small protein,或称微蛋白;microprotein或迷你蛋白miniprotein)检测困难等原因,小开放阅读框长期未得到充分注释和研究。...小开放阅读框(small open reading frame,sORF)广泛存在于不同生物基因组中,由于其序列短,以及编码的产物小蛋白(small protein,或称微蛋白;microprotein或迷你蛋白miniprotein)检测困难等原因,小开放阅读框长期未得到充分注释和研究。近年来,随着高通量测序、翻译组和质谱分析等技术的不断发展,在不同生物中发现大量新的小开放阅读框,其编码的小蛋白及介导的翻译调控已应用于药物开发及植物抗病机理等研究。但是,目前对微生物的小开放阅读框相关研究和应用还相对有限。本文综述了小开放阅读框编码产物小蛋白的发现和鉴定,以及上游开放阅读框(upstream open reading frame,uORF)对mRNA翻译调控等最新研究进展,重点介绍了微生物基因组中小开放阅读框的鉴定和功能研究进展,为深入认识微生物中小开放阅读框的功能和作用机制,以及植物和动物等高等其他生物的小蛋白和翻译调控相关研究提供参考。展开更多
Translational regulation is a critical step in the process of gene expression and governs the synthesis of proteins from mRNAs.Many studies have revealed translational regulation in plants in response to various envir...Translational regulation is a critical step in the process of gene expression and governs the synthesis of proteins from mRNAs.Many studies have revealed translational regulation in plants in response to various environmental stimuli.However,there have been no studies documenting the comprehensive landscape of translational regulation and allele-specific translational efficiency in multiple plant tissues,especially those of rice,a main staple crop that feeds nearly half of the world’s population.Here we used RNA sequencing and ribosome profiling data to analyze the transcriptome and translatome of an elite hybrid rice,Shanyou 63(SY63),and its parental varieties Zhenshan 97 and Minghui 63.The results revealed that gene expression patterns varied more among tissues than among varieties at the transcriptional and translational levels.We identified 3392 upstream open reading frames(uORFs),and the uORF-containing genes were enriched in transcription factors.Only 668 of 13492 long non-coding RNAs could be translated into peptides.Finally,we discovered numerous genes with allele-specific translational efficiency in SY63 and demonstrated that some cis-regulatory elements may contribute to allelic divergence in translational efficiency.Overall,these findings may improve our understanding of translational regulation in rice and provide information for molecular breeding research.展开更多
Small open reading frames(sORFs) are distributed over a wide variety of transcripts. sORFs encoding functional peptides have been identified in various configurations within apparently long noncoding RNAs. Many transl...Small open reading frames(sORFs) are distributed over a wide variety of transcripts. sORFs encoding functional peptides have been identified in various configurations within apparently long noncoding RNAs. Many translated sORFs have been identified across mRNAs, including 5’-upstream, coding domain, and 3’-downstream. sORFs have also been found in circular RNAs, pri-miRNAs, and ribosomal RNAs. Here, we present an overview of the wide distribution of the sORFs in transcripts and their functional roles in organisms.展开更多
文摘上游开放阅读框(upstream open reading frame, uORF)是一类能够精确控制蛋白质翻译的mRNA元件,位于mRNA的5'端前导区,主要通过抑制翻译起始来调节下游主体开放阅读框(main open reading frame, mORF)的翻译。目前对植物uORF的预测和鉴定主要集中于生物信息学和翻译组学鉴定技术。植物uORF广泛参与调节生长发育、营养代谢、抗病免疫等多个生命活动过程。本文对植物uORF的分类、功能机制、预测和鉴定方法、植物规避uORF的方式以及植物uORF的工程应用等进行综述归纳,旨在更系统和深入地理解植物uORF的功能与机制,并为uORF应用于作物分子育种工作提供参考。
基金supported by the National Natural Science Foundation of China(31861143004)the Agricultural Science and Technology Innovation Program of CAAS to Wen-Xue Li.
文摘Conventional peptides(CPs)and non-conventional peptides(NCPs)are generated from small open reading frames,but most CPs are derived from large precursors.NCPs,which are derived from sequences other than conventional open reading frames or annotated coding sequences regions,function in plant development and adaptation to stresses.Ribosome profiling,a technique for studying translational regulation,can be used to identify NCPs.Another new technique,peptidogenomics,which integrates mass spectrometry and genomics,is becoming more widely used for identifying plant NCPs.In recent years,numerous studies have investigated the roles in monocots and dicots of miRNA-derived peptides and upstream open reading frames,which have potential for improving agronomic traits.Investigating the biological functions of NCPs will advance molecular plant breeding by identifying regulators of plant growth and development.We present an overview of NCP identification methods and recent findings about NCP biological functions.
文摘Research Aims: Obesity and type 2 diabetes are known to be associated with increased risk of various types of cancer. However, the molecular biological mechanism of how the risk of cancer is increased in obesity or type 2 diabetes is not known. The aim this research is to investigate if the decreased expression of p27Kip1, a cell cycle repressor protein, plays a central role in this mechanism. Research Methods, Previous Studies and Theoretical Backgrounds: It is well known that the expression of p27Kip1 is increased by numerous nutritional or chemopreventive anti-cancer agents. But it has never been known that the expression of p27Kip1 could be decreased, rather than increased, and the risk of cancer could be increased, rather than decreased. This problem was solved recently and this new analytical method was used in this study. Results: 1) The expression of p27Kip1 was indeed significantly decreased in human obese type 2 diabetic individuals relative to the lean normal controls. 2) The expression of p27Kip1 was also significantly decreased in genetically obese rodents relative to the lean normal controls. Additionally, in obese rodents, the concentrations of glucose or insulin were significantly increased relative to the lean normal controls. 3) Using human cells cultured in vitro it was found that the increased concentrations of glucose or insulin decrease the expression of p27Kip1. Conclusions: These results suggest that higher concentrations of glucose or insulin increase the risk of various types of cancer in obesity or type 2 diabetes by decreasing the expression of p27Kip1.
文摘基因组中约有20%的基因具有上游开放阅读框(upstream open reading frame,uORF),它位于成熟mRNA 5'端非编码区(5'-UTR)。本文简介了uORF同源群的挖掘方法、分类和进化,以及调控下游mORF翻译的研究进展。植物(拟南芥和水稻等)和昆虫(果蝇等)基因组中普遍存在保守肽uORFs,并且在序列多样性方面有相似之处。但它们在平均长度、基因组聚类、与甲基转移酶的关联性上有所不同。植物uORF的长度通常短于昆虫uORF。借助拟南芥和水稻全长cDNA序列比较,不同的uORF同源群对其下游如转录因子,信号转导因子、发育信号分子和翻译起始因子eIF5等编码基因的mORF具有调控功能。对于真核生物基因组中包含CHCH域的uORF进行贝叶斯系统发育分析,结果表明,同源群8-like分属5个物种(绿藻、节肢动物、线虫、无脊椎动物和真菌)。在真核生物生长、发育和生理过程中,uORF通常作为反式因子对mORF表达起调节器作用,例如,在植物蔗糖、多胺、磷脂酰胆碱,以及甲基转移酶反应中,相当大比例的uORF参与介导mORF的翻译调控。
基金supported by grants from the National Natural Science Foundation of China(32070284)the Major Project of Hubei Hongshan Laboratory(2022hszd016)the Key Research and Development Program of Hubei Province(2022BFE003)to G.Xu.We apologize to colleagues whose excellent work was not cited in this review due to the space limit.
文摘Messenger RNA(mRNA)translation consists of initiation,elongation,termination,and ribosome recycling,carried out by the translation machinery,primarily including tRNAs,ribosomes,and translation factors(TrFs).Translational regulators transduce signals of growth and development,as well as biotic and abiotic stresses,to the translation machinery,where global or selective translational control occurs to modulate mRNA translation efficiency(TrE).As the basis of translational control,the translation machinery directly determines the quality and quantity of newly synthesized peptides and,ultimately,the cellular adaption.Thus,regulating the availability of diverse machinery components is reviewed as the central strategy of translational control.We provide classical signaling pathways(e.g.,integrated stress responses)and cellular behaviors(e.g.,liquideliquid phase separation)to exemplify this strategy within different physiological contexts,particularly during hostemicrobe interactions.With new technologies developed,further understanding this strategy will speed up translational medicine and translational agriculture.
基金supported by grants from the National Key R&D Program of China(2023ZD04073)the Major Project of Hubei Hongshan Laboratory(2022hszd016)+1 种基金the Key Research and Development Program of Hubei Province(2022BFE003)the National Natural Science Foundation of China(32070284)to G.Xu.
文摘A 5'-leader,known initially as the 5'-untranslated region,contains multiple isoforms due to alternative splicing(aS)and alternative transcription start site(aTSS).Therefore,a representative 5'-leader is demanded to examine the embedded RNA regulatory elements in controlling translation efficiency.Here,we develop a ranking algorithm and a deep-learning model to annotate representative 5'-leaders for five plant species.We rank the intra-sample and inter-sample frequency of aS-mediated transcript isoforms using the Kruskal-Wallis test-based algorithm and identify the representative aS-5'-leader.To further assign a representative 5'-end,we train the deep-learning model 5'leaderP to learn aTsS-mediated 5'-end distribution patterns from cap-analysis gene expression data.The model accurately predicts the 5'-end,confirmed experimentally in Arabidopsis and rice.The representative 5'-leader-contained gene models and 5'leaderP can be accessed at RNAirport(http:/www.rnairport.com/leader5P/).The Stage 1 annotation of 5'-leader records 5'-leader diversity and will pave the way to Ribo-Seq open-reading frame annotation,identical to the project recently initiated by human GENCODE.
文摘小开放阅读框(small open reading frame,sORF)广泛存在于不同生物基因组中,由于其序列短,以及编码的产物小蛋白(small protein,或称微蛋白;microprotein或迷你蛋白miniprotein)检测困难等原因,小开放阅读框长期未得到充分注释和研究。近年来,随着高通量测序、翻译组和质谱分析等技术的不断发展,在不同生物中发现大量新的小开放阅读框,其编码的小蛋白及介导的翻译调控已应用于药物开发及植物抗病机理等研究。但是,目前对微生物的小开放阅读框相关研究和应用还相对有限。本文综述了小开放阅读框编码产物小蛋白的发现和鉴定,以及上游开放阅读框(upstream open reading frame,uORF)对mRNA翻译调控等最新研究进展,重点介绍了微生物基因组中小开放阅读框的鉴定和功能研究进展,为深入认识微生物中小开放阅读框的功能和作用机制,以及植物和动物等高等其他生物的小蛋白和翻译调控相关研究提供参考。
基金supported by the National Natural Science Foundation of China(31871269 and 32270712)the Hubei Provincial Natural Science Foundation of China(2019CFA014)a starting research grant for High-level Talents from Guangxi University.
文摘Translational regulation is a critical step in the process of gene expression and governs the synthesis of proteins from mRNAs.Many studies have revealed translational regulation in plants in response to various environmental stimuli.However,there have been no studies documenting the comprehensive landscape of translational regulation and allele-specific translational efficiency in multiple plant tissues,especially those of rice,a main staple crop that feeds nearly half of the world’s population.Here we used RNA sequencing and ribosome profiling data to analyze the transcriptome and translatome of an elite hybrid rice,Shanyou 63(SY63),and its parental varieties Zhenshan 97 and Minghui 63.The results revealed that gene expression patterns varied more among tissues than among varieties at the transcriptional and translational levels.We identified 3392 upstream open reading frames(uORFs),and the uORF-containing genes were enriched in transcription factors.Only 668 of 13492 long non-coding RNAs could be translated into peptides.Finally,we discovered numerous genes with allele-specific translational efficiency in SY63 and demonstrated that some cis-regulatory elements may contribute to allelic divergence in translational efficiency.Overall,these findings may improve our understanding of translational regulation in rice and provide information for molecular breeding research.
基金supported by the Project Program of State Key Laboratory of Natural Medicines(No. SKLNMBZ201403)the National Science and Technology Major Projects of New Drugs (Nos.2012ZX09103301-004 and 2014ZX09508007) in ChinaThis project was also funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
文摘Small open reading frames(sORFs) are distributed over a wide variety of transcripts. sORFs encoding functional peptides have been identified in various configurations within apparently long noncoding RNAs. Many translated sORFs have been identified across mRNAs, including 5’-upstream, coding domain, and 3’-downstream. sORFs have also been found in circular RNAs, pri-miRNAs, and ribosomal RNAs. Here, we present an overview of the wide distribution of the sORFs in transcripts and their functional roles in organisms.