为了解拟南芥中Dicer-like蛋白对tRNA衍生的小RNA(tRNA-derived small RNAs,tsRNAs)的产生有何影响,对拟南芥野生型和不同Dicer-like(DCL)基因突变体进行tRNA-seq测序,并分析tsRNA和tRNA的表达量.结果显示,DCL4基因突变后tsRNA的表达量...为了解拟南芥中Dicer-like蛋白对tRNA衍生的小RNA(tRNA-derived small RNAs,tsRNAs)的产生有何影响,对拟南芥野生型和不同Dicer-like(DCL)基因突变体进行tRNA-seq测序,并分析tsRNA和tRNA的表达量.结果显示,DCL4基因突变后tsRNA的表达量明显降低,说明DCL4可能参与tsRNA的产生.拟南芥tRC1位点(Chr1:21268000-21310000)具有大量串联分布的tRNA序列,通过对RNA介导的甲基化(RdDM)途径相关基因CLSY1突变体中tRC1位点的24 nt siRNA和tsRNA进行分析,推断tRC1位点的tsRNA受RdDM途径负调控.综上,本研究鉴定到DCL4在tsRNA生成中的潜在作用,部分tsRNA的生成与RdDM途径有关.展开更多
目的探讨肝细胞内质网应激相关的tRNA衍生性小RNA(tRNA derived small RNA,tsRNA)表达谱及其功能特征。方法将AML12细胞随机分为对照组和高脂组,采用棕榈酸刺激高脂组,建立肝细胞内质网应激模型。以RT-qPCR和Western blot法检测内质网...目的探讨肝细胞内质网应激相关的tRNA衍生性小RNA(tRNA derived small RNA,tsRNA)表达谱及其功能特征。方法将AML12细胞随机分为对照组和高脂组,采用棕榈酸刺激高脂组,建立肝细胞内质网应激模型。以RT-qPCR和Western blot法检测内质网应激标志蛋白GRP78和CHOP的表达,油红O染色法观察脂滴生成情况。通过高通量测序技术检测tsRNA表达谱并筛选出差异基因。利用生物信息学分析预测差异tsRNA的靶基因,并通过GO分析和KEGG分析研究差异tsRNA的潜在功能。结果与对照组比较,棕榈酸干预导致高脂组GRP78和CHOP表达在mRNA及蛋白水平均显著升高(P<0.05),脂肪变性显著加重。tsRNA测序得到38条差异tsRNA(倍数变化>2,P<0.05)。GO分析显示,差异tsRNA的靶基因主要调控类黄酮代谢、葡萄糖醛酸代谢和岩藻糖基化等功能。KEGG分析显示,差异tsRNA的靶基因在戊糖和葡萄糖醛酸酯的相互转化、淀粉和蔗糖代谢、cAMP及Rap1等肝细胞代谢相关的信号通路中高度富集。结论内质网应激可显著改变肝细胞的tsRNA表达谱,其功能可能与调控肝脏糖代谢及生物转化作用有关。展开更多
Hepatocellular carcinoma(HCC),which makes up the majority of liver cancer,is induced by the infection of hepatitis B/C virus.Biomarkers are needed to facilitate the early detection of HCC,which is often diagnosed too ...Hepatocellular carcinoma(HCC),which makes up the majority of liver cancer,is induced by the infection of hepatitis B/C virus.Biomarkers are needed to facilitate the early detection of HCC,which is often diagnosed too late for effective therapy.The tRNA-derived small RNAs(tsRNAs)play vital roles in tumorigenesis and are stable in circulation.However,the diagnostic values and biological functions of circulating tsRNAs,especially for HCC,are still unknown.In this study,we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum.We identified tRF-Gln-TTG-006,which was remarkably upregulated in HCC serum(training cohort:24 HCC patients vs.24 healthy controls).In the validation stage,we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity(80.4%)and specificity(79.4%)even in the early stage(Stage I:sensitivity,79.0%;specificity,74.8%;155 healthy controls vs.153 HCC patients from two cohorts).Moreover,in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells,and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays.In summary,our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.展开更多
tsRNA(tRNA-derived small RNAs)是近几年受到高度关注的具有基因调节功能的一类非编码小RNA,其来源于tRNA,且属于tRNA在生理或病理条件下切割后产生的新的小RNA。早期有关tsRNAs结构和功能的研究认为,tsRNAs作为一种RNA损伤后的降解产...tsRNA(tRNA-derived small RNAs)是近几年受到高度关注的具有基因调节功能的一类非编码小RNA,其来源于tRNA,且属于tRNA在生理或病理条件下切割后产生的新的小RNA。早期有关tsRNAs结构和功能的研究认为,tsRNAs作为一种RNA损伤后的降解产物,只是随机的核苷酸序列,本身没有与生理代谢过程相关的结构或功能特性;同时,由于这些small non-cpdomg RNA片段数量太少,推测其对早期胚胎发育并不发挥重要作用。展开更多
随着测序技术的发展和对tRNA衍生小分子(tRNA-derived small RNA,tsRNAs)的深入研究,越来越多的tsRNAs及其功能在各物种中被鉴定。tsRNAs根据切割位点的不同可分为tRNA衍生片段(tRNA-derived fragment,tRF)和tRNA应激诱导RNA(tRNA-deriv...随着测序技术的发展和对tRNA衍生小分子(tRNA-derived small RNA,tsRNAs)的深入研究,越来越多的tsRNAs及其功能在各物种中被鉴定。tsRNAs根据切割位点的不同可分为tRNA衍生片段(tRNA-derived fragment,tRF)和tRNA应激诱导RNA(tRNA-derived stress-induced RNA,tiRNA),其中tRF是一类具有调节功能的非编码RNA。为了加深对tRF的研究,近年来一些基于测序数据的tRF鉴定方法和相关数据库不断涌现,前者主要包括Telonis等人的算法和tDRmapper方法,后者主要有tRFdb、tRF2Cancer和MINTbase等。同时这两者为tRF的深入研究提供了更有效的工具。大量的研究表明,tRF主要以类似miRNA的方式对RNA、DNA及蛋白质进行调节,但也存在特异的作用方式。随着对这三者的深入研究,研究人员发现tRF在人类疾病的各种生物过程中也扮演着重要的角色,例如可以作为生物标志物。因此本文主要对tRF的鉴定方法、数据库、对靶分子的调节机制及其与人类疾病的关系作一综述。展开更多
转运RNA衍生小RNA(tRNA-derived small RNAs, tsRNAs)是一类来源于tRNAs的新型非编码小RNA,广泛存在于动物、植物的组织细胞以及体液中,在胚胎发育、细胞命运决定、机体免疫调控、获得性遗传以及包括癌症在内的多种人类疾病的发生发展...转运RNA衍生小RNA(tRNA-derived small RNAs, tsRNAs)是一类来源于tRNAs的新型非编码小RNA,广泛存在于动物、植物的组织细胞以及体液中,在胚胎发育、细胞命运决定、机体免疫调控、获得性遗传以及包括癌症在内的多种人类疾病的发生发展中发挥着不可或缺的作用。然而,由于tsRNAs含有从其tRNAs前体继承而来的多种RNA修饰,这些RNA修饰一方面增加了tsRNAs信息编码的深度,丰富了tsRNAs在细胞内功能和作用机制的多样性,另一方面也增加了其功能研究的复杂性。近年来, tsRNAs的作用机制成为该领域的研究焦点和关键点。该文系统性地综述了tsRNAs的最新研究进展,包括其生成途径、检测方法、作用机制以及生物学功能的多样性,并探讨了tsRNAs作为生物标志物在临床疾病诊断中的应用前景。展开更多
With the development of sequencing technology,transfer RNA(tRNA)-derived small RNAs(tsRNAs)have received extensive attention as a new type of small noncoding RNAs.Based on the differences in the cleavage sites of nucl...With the development of sequencing technology,transfer RNA(tRNA)-derived small RNAs(tsRNAs)have received extensive attention as a new type of small noncoding RNAs.Based on the differences in the cleavage sites of nucleases on tRNAs,tsRNAs can be divided into two categories,tRNA halves(tiRNAs)and tRNA-derived fragments(tRFs),each with specific subcellular localizations.Additionally,the biogenesis of tsRNAs is tissue-specific and can be regulated by tRNA modifications.In this review,we first elaborated on the classification and biogenesis of tsRNAs.After summarizing the latest mechanisms of tsRNAs,including transcriptional gene silencing,post-transcriptional gene silencing,nascent RNA silencing,translation regulation,rRNA regulation,and reverse transcription regulation,we explored the representative biological functions of tsRNAs in tumors.Furthermore,this review summarized the clinical value of tsRNAs in cancers,thus providing theoretical support for their potential as novel biomarkers and therapeutic targets.展开更多
Gastric cancer(GC)is one of the most common gastrointestinal tumors.As a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in cancer.Our previous studies...Gastric cancer(GC)is one of the most common gastrointestinal tumors.As a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in cancer.Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC.In this work,we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation,migration,and invasion of GC cells in vitro.The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3'untranslated region(UTR)site of acyl-coenzyme A dehydrogenase short/branched chain(ACADSB).In addition,ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells.Next,we used Gene Ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis.Finally,we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level,as well as the changes in reactive oxygen species(ROS)levels by flow cytometry.In summary,this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB,thereby promoting GC progression.It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens upnew possibilities for treatment.展开更多
文摘为了解拟南芥中Dicer-like蛋白对tRNA衍生的小RNA(tRNA-derived small RNAs,tsRNAs)的产生有何影响,对拟南芥野生型和不同Dicer-like(DCL)基因突变体进行tRNA-seq测序,并分析tsRNA和tRNA的表达量.结果显示,DCL4基因突变后tsRNA的表达量明显降低,说明DCL4可能参与tsRNA的产生.拟南芥tRC1位点(Chr1:21268000-21310000)具有大量串联分布的tRNA序列,通过对RNA介导的甲基化(RdDM)途径相关基因CLSY1突变体中tRC1位点的24 nt siRNA和tsRNA进行分析,推断tRC1位点的tsRNA受RdDM途径负调控.综上,本研究鉴定到DCL4在tsRNA生成中的潜在作用,部分tsRNA的生成与RdDM途径有关.
文摘目的探讨肝细胞内质网应激相关的tRNA衍生性小RNA(tRNA derived small RNA,tsRNA)表达谱及其功能特征。方法将AML12细胞随机分为对照组和高脂组,采用棕榈酸刺激高脂组,建立肝细胞内质网应激模型。以RT-qPCR和Western blot法检测内质网应激标志蛋白GRP78和CHOP的表达,油红O染色法观察脂滴生成情况。通过高通量测序技术检测tsRNA表达谱并筛选出差异基因。利用生物信息学分析预测差异tsRNA的靶基因,并通过GO分析和KEGG分析研究差异tsRNA的潜在功能。结果与对照组比较,棕榈酸干预导致高脂组GRP78和CHOP表达在mRNA及蛋白水平均显著升高(P<0.05),脂肪变性显著加重。tsRNA测序得到38条差异tsRNA(倍数变化>2,P<0.05)。GO分析显示,差异tsRNA的靶基因主要调控类黄酮代谢、葡萄糖醛酸代谢和岩藻糖基化等功能。KEGG分析显示,差异tsRNA的靶基因在戊糖和葡萄糖醛酸酯的相互转化、淀粉和蔗糖代谢、cAMP及Rap1等肝细胞代谢相关的信号通路中高度富集。结论内质网应激可显著改变肝细胞的tsRNA表达谱,其功能可能与调控肝脏糖代谢及生物转化作用有关。
基金This study was supported by the Training Program of the Major Research Plan of the National Natural Science Foundation of China(No.92049109)the National Natural Science Foundation of China(Nos.32000549 and 82003024)+1 种基金the Natural Science Foundation of Jiangsu Province(No.BK2020041989)the Natural Science Foundation of Nanjing University of Chinese Medicine(No.NZY82003024).
文摘Hepatocellular carcinoma(HCC),which makes up the majority of liver cancer,is induced by the infection of hepatitis B/C virus.Biomarkers are needed to facilitate the early detection of HCC,which is often diagnosed too late for effective therapy.The tRNA-derived small RNAs(tsRNAs)play vital roles in tumorigenesis and are stable in circulation.However,the diagnostic values and biological functions of circulating tsRNAs,especially for HCC,are still unknown.In this study,we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum.We identified tRF-Gln-TTG-006,which was remarkably upregulated in HCC serum(training cohort:24 HCC patients vs.24 healthy controls).In the validation stage,we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity(80.4%)and specificity(79.4%)even in the early stage(Stage I:sensitivity,79.0%;specificity,74.8%;155 healthy controls vs.153 HCC patients from two cohorts).Moreover,in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells,and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays.In summary,our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.
文摘tsRNA(tRNA-derived small RNAs)是近几年受到高度关注的具有基因调节功能的一类非编码小RNA,其来源于tRNA,且属于tRNA在生理或病理条件下切割后产生的新的小RNA。早期有关tsRNAs结构和功能的研究认为,tsRNAs作为一种RNA损伤后的降解产物,只是随机的核苷酸序列,本身没有与生理代谢过程相关的结构或功能特性;同时,由于这些small non-cpdomg RNA片段数量太少,推测其对早期胚胎发育并不发挥重要作用。
文摘转运RNA衍生小RNA(tRNA-derived small RNAs, tsRNAs)是一类来源于tRNAs的新型非编码小RNA,广泛存在于动物、植物的组织细胞以及体液中,在胚胎发育、细胞命运决定、机体免疫调控、获得性遗传以及包括癌症在内的多种人类疾病的发生发展中发挥着不可或缺的作用。然而,由于tsRNAs含有从其tRNAs前体继承而来的多种RNA修饰,这些RNA修饰一方面增加了tsRNAs信息编码的深度,丰富了tsRNAs在细胞内功能和作用机制的多样性,另一方面也增加了其功能研究的复杂性。近年来, tsRNAs的作用机制成为该领域的研究焦点和关键点。该文系统性地综述了tsRNAs的最新研究进展,包括其生成途径、检测方法、作用机制以及生物学功能的多样性,并探讨了tsRNAs作为生物标志物在临床疾病诊断中的应用前景。
基金supported by grants from the National Natural Science Foundation of China(No.81871720,82072363)the Nantong Municipal Health Commission,Jiangsu,China(No.QA2020027).
文摘With the development of sequencing technology,transfer RNA(tRNA)-derived small RNAs(tsRNAs)have received extensive attention as a new type of small noncoding RNAs.Based on the differences in the cleavage sites of nucleases on tRNAs,tsRNAs can be divided into two categories,tRNA halves(tiRNAs)and tRNA-derived fragments(tRFs),each with specific subcellular localizations.Additionally,the biogenesis of tsRNAs is tissue-specific and can be regulated by tRNA modifications.In this review,we first elaborated on the classification and biogenesis of tsRNAs.After summarizing the latest mechanisms of tsRNAs,including transcriptional gene silencing,post-transcriptional gene silencing,nascent RNA silencing,translation regulation,rRNA regulation,and reverse transcription regulation,we explored the representative biological functions of tsRNAs in tumors.Furthermore,this review summarized the clinical value of tsRNAs in cancers,thus providing theoretical support for their potential as novel biomarkers and therapeutic targets.
基金was supported by the National Natural Science Foundation of China(Nos.82272411 and 82072363)the Jiangsu Provincial Medical Key Discipline(Laboratory)(No.ZDXK202240)the Science and Technology Project of Jiangsu Province(No.BE2023741),China。
文摘Gastric cancer(GC)is one of the most common gastrointestinal tumors.As a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in cancer.Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC.In this work,we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation,migration,and invasion of GC cells in vitro.The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3'untranslated region(UTR)site of acyl-coenzyme A dehydrogenase short/branched chain(ACADSB).In addition,ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells.Next,we used Gene Ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis.Finally,we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level,as well as the changes in reactive oxygen species(ROS)levels by flow cytometry.In summary,this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB,thereby promoting GC progression.It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens upnew possibilities for treatment.
